Papers - MORITAKE Hiroshi
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Novel SKIC3 variants in tricho-hepato-enteric syndrome with hemochromatosis Reviewed
Ochiai K., Aoki Y., Yamada N., Aman M., Yamashita A., Yamaguchi M., Nakato D., Takenouchi T., Kosaki K., Kodama Y., Moritake H.
Human Genome Variation 12 ( 1 ) 14 2025.12
Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Human Genome Variation
Tricho-hepato-enteric syndrome (THES), a rare autosomal recessive disorder caused by variants in the SKIC3 or SKIC2 gene, is characterized by intractable diarrhea, woolly hair, growth restriction and liver disease. Here we report a neonatal case of THES with neonatal hemochromatosis, in which the novel compound heterozygous SKIC3 variants NM_014639.4:c.815_816del p.(Gly272AlafsTer9) and NM_014639.4:c.2284G>A p.(Gly762Arg) were identified. Further research is needed to elucidate the mechanisms underlying iron metabolism dysregulation in THES.
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Age-specific mutation profiles and their prognostic implications in pediatric KMT2A-rearranged acute myeloid leukemia. Reviewed
Shoji K, Yoshida K, Iyoda S, Ishikawa M, Tanaka M, Nobe M, Saito N, Shino Y, Nannya Y, Yamato G, Tsujimoto S, Shiba N, Hayashi Y, Shiozawa Y, Shiraishi Y, Chiba K, Okada A, Tanaka H, Miyano S, Koga Y, Goto H, Terui K, Ito E, Kiyokawa N, Tomizawa D, Taga T, Moritake H, Tawa A, Takita J, Nishikori M, Adachi S, Ogawa S, Matsuo H
Haematologica 2025.10
Language：English Publishing type：Research paper (scientific journal)
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Interference of Intravenous Acetaminophen with Continuous Glucose Monitoring System Reviewed
Matsuyama Misayo, Meiri Satoru, Sawada Hirotake, Masuya Ryuta, Nakame Kazuhiko, Moritake Hiroshi
JMA Journal 8 ( 4 ) 1463 - 1467 2025.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Medical Association / The Japanese Associaiton of Medical Sciences
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盛武 浩
Frontiers in Hematology 4 1668408 2025.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA
Background: Epigenetic dysregulation plays a central role in pediatric acute myeloid leukemia (AML), yet its clinical relevance remains underexplored. This study primarily aimed to elucidate the clinical effect of H3K27me3 and H3K4me3 status on pediatric acute myeloid leukemia. We evaluated the prognostic impact of H3K27me3 and H3K4me3 histone trimethylation, along with associated gene expression profiles, in pediatric AML. Methods: We retrospectively analyzed 74 children with newly diagnosed non-FAB M3 and non-Down syndrome AML in a prolonged cohort in Japan. Bone marrow immunohistochemistry assessed H3K27me3 and H3K4me3 expression levels. RNA sequencing was successfully performed on sorted leukemic blasts in six representative cases, owing to limited sample availability. Chemoresistance and epigenetic modulation were evaluated in AML cell lines treated with GSK-J4, a histone demethylase inhibitor. Results: High H3K27me3 expression at diagnosis was significantly associated with superior overall and event-free survival over three years (OS HR 8.0; EFS HR 5.0; both p < 0.01). H3K4me3 levels at diagnosis showed no prognostic impact. Among 14 KMT2A-rearranged cases, all six patients with high H3K27me3 achieved a long-term first remission (median follow-up: 10 years), whereas those with low expression had higher relapse rates. Transcriptomic analysis revealed upregulation of HOXA9, and HOXA-cluster genes and downregulation of ABCB1, in low H3K27me3 samples. In vitro, GSK-J4 increased H3K27me3 and suppressed HOXA9 expression in KG-1 cells, enhancing sensitivity to cytarabine. Conclusion: Low H3K27me3 expression defines a poor-risk group in pediatric AML, potentially via HOXA9-driven dysregulation. H3K27me3 may serve as a prognostic biomarker and potential therapeutic target.
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Yamamoto N, Maeda K, Kimoto Y, Moritake H
BMJ case reports 18 ( 8 ) 2025.8
Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：BMJ Case Reports
Rasmussen encephalitis (RE) is a progressive disease characterised by unilateral brain atrophy, drug-resistant epilepsy, epilepsia partialis continua, hemiparesis and cognitive decline. Early initiation of immunomodulatory therapy is crucial to slow disease progression. However, early formal diagnosis is challenging as it typically requires hemispheric atrophy or brain biopsy. This case reports on a preschool-aged boy with RE who began immunotherapy before demonstrating clear hemispheric atrophy. Follow-up MRI did not indicate global hemispheric atrophy; however, FreeSurfer-based volumetric analysis revealed a decreased left:right hemispheric volume ratio, suggesting early left hemispheric atrophy. Subsequently, intensive immunotherapy was administered. Over 3 years of treatment, the patient exhibited gradual hemispheric atrophy on MRI, along with mild motor and cognitive impairments. Serial FreeSurfer-based volumetric analysis may contribute to detecting subtle hemispheric volume changes in RE, facilitating prompt diagnosis and early initiation of immunotherapy - potentially limiting disease progression.
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Novel SKIC3 variants in tricho-hepato-enteric syndrome with hemochromatosis Reviewed
青木 良則, 阿萬 紫, 山下 篤, 山口 昌俊, 児玉 由紀, 盛武 浩
Human Genome Variation 12 14 2025.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Nature
Tricho-hepato-enteric syndrome (THES), a rare autosomal recessive disorder caused by variants in the SKIC3 or SKIC2 gene, is characterized by intractable diarrhea, woolly hair, growth restriction and liver disease. Here we report a neonatal case of THES with neonatal hemochromatosis, in which the novel compound heterozygous SKIC3 variants NM_014639.4:c.815_816del p.(Gly272AlafsTer9) and NM_014639.4:c.2284G>A p.(Gly762Arg) were identified. Further research is needed to elucidate the mechanisms underlying iron metabolism dysregulation in THES.
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Fauzi YR, Nakahata S, Shimoda K, Matsuura T, Hagiwara S, Inoue K, Moritake H, Morishita K
Biochemical and biophysical research communications 756 151564 2025.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
Previously, we developed a complete human IgG TFR1 antibody (JST-TFR09/PPMX-T003) that showed a potentially practical therapeutic effect against adult T-cell leukemia/lymphoma (ATLL) in vitro and in vivo. In the present study, to elucidate the molecular mechanism underlying ATLL cell death induced by anti-TFR1 antibodies, we performed comprehensive gene expression analysis and mass spectrometry on ATLL cells treated with PPMX-T003 antibody. These results suggest that PPMX-T003 antibody treatment of ATLL cell lines induces ferroptosis mediated by ferritin degradation. PPMX-T003 antibody-treated ATLL cell lines showed a decrease in ferritin proteins, an increase in ferrous iron (Fe2+), reactive oxygen species (ROS) generation, and malondialdehyde as induction of lipid peroxidation. Moreover, treatment with a ferroptosis inhibitor (ferroportin-1) inhibited the cell death induced by PPMX-T003 antibody in ATLL cells. Furthermore, NCO4A and LC3-II were induced following antibody treatment, and ferritin degradation was inhibited by lysosomal inhibitors, suggesting that ferritin degradation depends on autolysosomal system activation. Here, we introduce ferroptosis as one of the potential mechanisms of PPMX-T003 antibody, which is promising for future therapeutic antibodies targeting a wide range of leukemia and cancers, including ATLL.
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Aoki Y., Kota Y., Shimada M., Taniguchi T., Yamauchi S., Matsusaka M., Hamasuna K., Watanabe Y., Kodama Y., Moritake H.
Children 12 ( 2 ) 2025.2
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Children
Background: Preterm infants often have unstable vital signs and prolonged hospital stays that can hinder parent–infant bonding, especially under COVID-19 restrictions. This study aimed to evaluate whether listening to songs recorded by parents was effective in stabilizing the condition of premature infants. Methods: This randomized controlled study was conducted at the University of Miyazaki Hospital from October 2022 to March 2024 during the COVID-19 pandemic period. The participants were preterm infants born at less than 33 weeks gestation and their parents, all of whom recorded songs. The recorded songs were played daily to the infants in the intervention group, while the control group received usual care. Primary outcomes included vital signs (respiratory rate, pulse oximetry saturation, heart rate) and activity level. Results: Data for 33 preterm infants (intervention, n = 17 [total 749 sessions]; control, n = 16 [total 721 sessions]) were analyzed for changes in vital signs and activity levels. The intervention reduced infants’ respiratory rates (4.1 [95% CI: 2.5–5.6], p < 0.001) and slightly but statistically significantly increased pulse oximetry saturation (0.6 [95% CI: 0.02–1.2], p < 0.044). Conclusions: Recorded parental songs were found to safely stabilize the respiratory status of preterm infants and may serve as an accessible intervention to support parent–infant attachment, particularly in settings with restricted parental visitation.
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Mori K., Maeda K., Kimoto Y., Ikeda T., Honda R., Yoshiura K.I., Moritake H.
Pediatrics International 67 ( 1 ) e70171 2025.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Pediatrics International
DOI： 10.1111/ped.70171
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Lymphatic dysplasia evaluated by indocyanine green lymphography in congenital myotonic dystrophy Reviewed
Tate M., Aoki Y., Ochiai K., Kodama Y., Nakame K., Kodama Y., Moritake H.
Pediatrics International 67 ( 1 ) e70170 2025.1
Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Pediatrics International
DOI： 10.1111/ped.70170
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Yokoyama R., Kodama Y., Takamura K., Takahashi M., Tanaka M., Watanabe N., Moritake H.
Journal of Cardiology Cases 31 ( 6 ) 155 - 157 2025
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cardiology Cases
Exercise stress echocardiography (ESE) is a feasible and valuable tool for evaluating subclinical pulmonary hypertension (PH). However, its utility in patients with unilateral pulmonary branch stenosis remains unclear. We present a case involving a 17-year-old patient with left pulmonary branch stenosis who exhibited exercise-induced PH in the contralateral pulmonary artery as detected by ESE. Standard echocardiography was unable to visualize the left pulmonary artery clearly; therefore, computed tomography was performed, revealing a left pulmonary branch stenosis with a minimum diameter of 4.2 mm. Resting echocardiography showed a pressure gradient of 17 mmHg, calculated using the tricuspid regurgitant velocity. During ESE with a prone ergometer, the slope of the mean pulmonary arterial pressure to systemic cardiac output was 3.1 mmHg/L/min, meeting the diagnostic criteria for exercise-induced PH. The patient underwent stent implantation to treat the left pulmonary branch stenosis. Follow-up ESE demonstrated improvement, with the slope of the mean pulmonary arterial pressure to systemic cardiac output decreasing to 1.5 mmHg/L/min. These findings underscore that ESE is both feasible and effective for assessing subclinical unilateral pulmonary branch stenosis. Learning objective: Patients with congenital unilateral peripheral branch pulmonary artery stenosis usually do not have pulmonary hypertension at rest, and identifying patients who require treatment is challenging. Exercise stress echocardiography can detect latent pulmonary hypertension of the contralateral pulmonary artery in some patients, providing valuable insights for determining treatment indications and evaluating the efficacy of catheter interventions for the stenotic lesion.
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Takahashi H., Tanaka S., Yuza Y., Iijima-Yamashita Y., Hasegawa D., Moritake H., Terui K., Iwamoto S., Shimada A., Matsubayashi J., Deguchi T., Hashii Y., Kiyokawa N., Miyachi H., Saito A.M., Taga T., Adachi S., Tomizawa D.
International Journal of Hematology 2025
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) has been shown to be effective in both adult and pediatric patients with acute promyelocytic leukemia (APL). Addition of ATO to conventional chemotherapy could lead to a reduction in the doses of cytotoxic agents, but the long-term safety of ATO is not fully understood, especially in children. The Japan Children’s Cancer Group conducted a risk-stratified prospective study to investigate safety and efficacy of ATO in children with newly diagnosed APL by replacing all three intensification phases with ATO. The 3-year event-free survival and overall survival rates in 27 children were 96.3% (95% CI 76.5%–99.5%) and 100% (95% CI 87.2%–100%), respectively. Prolonged QTc interval or other cardiac conduction disorders of any grade were observed in 20 out of the 63 intensification cycles. The durations of leukocytopenia, neutropenia, and G-CSF treatment were significantly shorter in this study than in a previous Japanese study that used conventional cytotoxic chemotherapy. Furthermore, no cardiac, metabolic, renal, cutaneous, or neurological symptoms were reported for up to 5 years after completion of the protocol therapy. The JPLSG AML-P13 study demonstrated excellent outcomes and safety of ATO in children with APL.
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Severe sinusoidal obstruction syndrome successfully treated with extracorporeal ultrafiltration method Reviewed
Wakamatsu Fumito, Kurogi Jun, Ebihara Shusei, Sakaguchi Hiromi, Nagasawa Shun, Nakagawa Midori, Yamada Ai, Tanaka Etsuko, Kinoshita Mariko, Konomoto Takao, Moritake Hiroshi
Japanese journal of pediatric nephrology 38 ( 0 ) n/a 2025
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society for Pediatric Nephrology
Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation, characterized by diuretic-resistant edema and weight gain. Severe cases can progress to multiple organ failure due to abdominal compartment syndrome, and the mortality rate remains high even with defibrotide, a known effective treatment for SOS.We present a case of severe SOS in a patient who was treated with extracorporeal ultrafiltration (ECUM) as part of continuous renal replacement therapy (CRRT). The patient received defibrotide immediately upon diagnosis of SOS following peripheral hematopoietic stem cell transplantation; however, he subsequently developed severe ascites and respiratory distress. Initiation of ECUM led to rapid improvement in fluid overload, including ascites, along with increased urine output. The patient was successfully weaned off ECUM within a short period, and his SOS symptoms improved. This case suggests that ECUM may effectively alleviate ascites related to SOS.Effective management of fluid overload is critical in the treatment of SOS. Regardless of renal function, close monitoring of fluid volume using percentage fluid overload (%FO) is essential, and CRRT should be initiated promptly based on the patient’s clinical status. ECUM may serve as an effective treatment option for managing SOS-related fluid overload.
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Re-evaluating the MYH9 p.I1816V variant in a patient with atypical clinical presentation Reviewed
Konomoto T., Wakamatsu F., Sakaguchi H., Kurogi J., Tanaka E., Moritake H.
Pediatric Nephrology 2025
Language：English Publishing type：Research paper (scientific journal) Publisher：Pediatric Nephrology
MYH9-related disease (MYH9-RD) is an autosomal dominant disorder typically characterized by macrothrombocytopenia, leukocyte inclusion bodies, and variable non-hematologic manifestations such as hearing loss and nephropathy. We herein describe a 16-year-old boy presenting with persistent proteinuria and biopsy-proven membranous nephropathy with focal segmental sclerosis. Genetic testing identified a rare MYH9 variant (p.I1816V), previously reported in association with Epstein syndrome. However, the patient had normal platelet counts, no leukocyte inclusions, and no abnormalities in non-muscle myosin heavy chain IIA (NMMHC-IIA) expression in neutrophils or podocytes. Although globally rare, the p.I1816V variant is more frequent in East Asian populations and is predicted to be benign by multiple in silico tools. This case illustrates the challenges of interpreting rare variants in the absence of supportive clinical findings and highlights the need for cautious evaluation in the era of next-generation sequencing.
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Goto H., Suenobu S., Koga Y., Yamamoto S., Nakashima K., Oba U., Hasegawa D., Usami I., Yamamori A., Moritake H., Nobusawa S., Okuno K., Kawaguchi K., Kanno M., Ishida H., Cho Y., Nishida H., Tomizawa D., Ihara K., Ohga S.
Frontiers in Hematology 4 2025
Publishing type：Research paper (scientific journal) Publisher：Frontiers in Hematology
Background: Epigenetic dysregulation plays a central role in pediatric acute myeloid leukemia (AML), yet its clinical relevance remains underexplored. This study primarily aimed to elucidate the clinical effect of H3K27me3 and H3K4me3 status on pediatric acute myeloid leukemia. We evaluated the prognostic impact of H3K27me3 and H3K4me3 histone trimethylation, along with associated gene expression profiles, in pediatric AML. Methods: We retrospectively analyzed 74 children with newly diagnosed non-FAB M3 and non-Down syndrome AML in a prolonged cohort in Japan. Bone marrow immunohistochemistry assessed H3K27me3 and H3K4me3 expression levels. RNA sequencing was successfully performed on sorted leukemic blasts in six representative cases, owing to limited sample availability. Chemoresistance and epigenetic modulation were evaluated in AML cell lines treated with GSK-J4, a histone demethylase inhibitor. Results: High H3K27me3 expression at diagnosis was significantly associated with superior overall and event-free survival over three years (OS HR 8.0; EFS HR 5.0; both p < 0.01). H3K4me3 levels at diagnosis showed no prognostic impact. Among 14 KMT2A-rearranged cases, all six patients with high H3K27me3 achieved a long-term first remission (median follow-up: 10 years), whereas those with low expression had higher relapse rates. Transcriptomic analysis revealed upregulation of HOXA9, and HOXA-cluster genes and downregulation of ABCB1, in low H3K27me3 samples. In vitro, GSK-J4 increased H3K27me3 and suppressed HOXA9 expression in KG-1 cells, enhancing sensitivity to cytarabine. Conclusion: Low H3K27me3 expression defines a poor-risk group in pediatric AML, potentially via HOXA9-driven dysregulation. H3K27me3 may serve as a prognostic biomarker and potential therapeutic target.
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CFAP43 variant in persistent respiratory symptoms after hematopoietic cell transplantation Reviewed
Nagasawa S., Nishimura T., Yamada A., Kamimura S., Ishimura M., Moritake H.
Human Genome Variation 11 ( 1 ) 41 2024.12
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Human Genome Variation
We describe a case of RAS-associated autoimmune leukoproliferative disease with primary ciliary dyskinesia (PCD)-like symptoms, such as recurrent pneumonia, sinusitis, and otitis media, that occurred 7 years after hematopoietic cell transplantation. Whole-exome sequencing revealed a heterozygous CFAP43 nonsense variant. Environmental factors related to hematopoietic cell transplantation may have led to PCD symptoms in this patient with this variant. Genetic screening can help avoid subsequent complications during patient management.
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Mitochondrial dynamics as a potential therapeutic target in acute myeloid leukemia Reviewed
Kinoshita M., Saito Y., Otani K., Uehara Y., Nagasawa S., Nakagawa M., Yamada A., Kamimura S., Moritake H.
International Journal of Hematology 120 ( 5 ) 601 - 612 2024.11
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Acute myeloid leukemia (AML) cells are highly dependent on oxidative phosphorylation and the mitochondrial dynamics regulated by fusion-related genes MFN1, MFN2, and OPA1 and fission-related genes DNM1L and MFF. An analysis of previously published gene expression datasets showed that high expression of MFF was significantly associated with poor prognosis in patients with AML. Based on this finding, we investigated the impact of mitochondrial dynamics in AML. Transduction of shRNA against fission-related genes, DNM1L and MFF, inhibited growth and increased the mitochondrial area in AML cell lines. Extracellular flux analysis showed that deletion of mitochondrial dynamic regulators reduced mitochondrial respiration without significantly affecting glycolysis, except in shDNM1L-transfected cells. Immunodeficient NOG mice transplanted with DNM1L- or MFF-knockdown AML cells survived significantly longer than controls. Treatment of AML cell lines with Mdivi-1, which inhibits the DRP1 encoded by DNM1L, inhibited cell proliferation and oxidative phosphorylation. Our results show that mitochondrial dynamics play an important role in AML, and provide novel biological insights. The inhibition of mitochondrial dynamics induces unique mitochondrial alterations, which may be explored as a potential therapeutic target in AML.
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HDAC Inhibitors Induce HLA Class I Molecules through the SOX10–IRF1 Axis in Clear Cell Sarcoma Cells Reviewed
Nguyen Minh Thi, Kikuchi Ryota, Nishibu Soshi, Zhou Yue, Moritake Hiroshi, Nakamura Takuro, Outani Hidetatsu, Hayashi Ryuji, Sakurai Hiroaki, Yokoyama Satoru
Biological and Pharmaceutical Bulletin 47 ( 11 ) 1913 - 1919 2024.11
Language：English Publishing type：Research paper (scientific journal) Publisher：The Pharmaceutical Society of Japan
Although immune checkpoint inhibitors (ICIs) are an effective treatment for clear cell sarcoma (CCS), a rare melanocytic sarcoma with a poor prognosis, their efficacies are still limited. Therefore, a novel therapeutic strategy is required to improve the efficacy of ICIs. We previously reported that histone deacetylase (HDAC) inhibitors increased melanoma immunogenicity through the SOX10–IRF1 pathway and may improve the efficacy of ICIs for melanoma. We herein demonstrated that the inhibition of HDAC induced the expression of HLA class I molecules through IRF1 in CCS cells, similar to melanoma. The suppression of SOX10 by small interfering RNA (siRNA) induced the expression of HLA class I molecules. In addition, the isoform-specific inhibition of HDAC1/3 induced the expression of another IRF1 downstream molecule, PD-L1 in CCS cells in concert with the suppression of SOX10. Furthermore, the knockdown of IRF1 impaired the induction of PD-L1 expression in CCS cells. Therefore, the inhibition of HDAC1/3 has potential as a novel strategy to increase immunogenicity and as combination therapy with ICIs for CCS and melanoma.
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Isolated Blind-Ended Major Aortic Pulmonary Collateral Artery With an Aneurysm in an Infant With Trisomy 21. Reviewed
Yonaga R, Kodama Y, Takamura K, Harada M, Moritake H
Cureus 16 ( 10 ) e72078 2024.10
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)
DOI： 10.7759/cureus.72078
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Kato S, Nakashima K, Yamato G, Saito S, Taneyama Y, Yamamoto N, Miyamura T, Kato K, Sato Y, Yamada A, Kamiya T, Nishikawa T, Uemura S, Tomizawa D, Moritake H, Terui K, Taga T, Hasegawa D
Pediatric blood & cancer 71 ( 10 ) e31244 2024.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Pediatric Blood and Cancer
Hypomethylating agent treatment for myeloid leukemia associated with Down syndrome (ML-DS) has been scarcely reported. Herein, we collected information on azacitidine treatment for ML-DS in Japan. Forty-eight cycles of azacitidine treatment were performed for 12 patients, including 11 relapsed or refractory (R/R) patients. In 40 cycles, azacitidine was used as monotherapy. No azacitidine-related death was observed. One cycle concurrently administered with methotrexate-based intrathecal therapy was discontinued due to toxicities. Only 4 of the 19 cycles given in non-remission achieved complete or partial remission. In conclusion, although most toxicities were acceptable, azacitidine monotherapy might be insufficient for R/R ML-DS cases.
DOI： 10.1002/pbc.31244
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KRAS G12 mutations as adverse prognostic factors in KMT2A-rearranged acute myeloid leukemia Reviewed
Iyoda S, Yoshida K, Shoji K, Ito N, Tanaka M, Nannya Y, Yamato G, Tsujimoto S, Shiba N, Hayashi Y, Shiozawa Y, Shiraishi Y, Chiba K, Okada A, Tanaka H, Miyano S, Koga Y, Goto H, Moritake H, Terui K, Ito E, Kiyokawa N, Tomizawa D, Taga T, Tawa A, Takita J, Nishikori M, Adachi S, Ogawa S, Matsuo H.
Leukemia 38 ( 7 ) 1609 - 1612 2024.7
Publishing type：Research paper (scientific journal)
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Nakame Kazuhiko, Masuya Ryuta, Nakazawa Shun, Nakagawa Midori, Yamada Ai, Kinoshita Mariko, Kamimura Sachiyo, Moritake Hiroshi, Ieiri Satoshi, Nanashima Atushi
Journal of the Japanese Society of Pediatric Surgeons 60 ( 2 ) 158 - 165 2024.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Pediatric Surgeons
<i>Purpose</i>: Central venous catheters (CVCs) are used in the treatment of pediatric hematological and oncological diseases. Recently, the ultrasound (US)-guided supraclavicular approach to brachiocephalic vein cannulation with in-plane views has been described as a safe central venous catheterization technique.<i>Methods</i>: A retrospective study was performed on patients who underwent US-guided tunneled CVC insertion into the internal jugular vein with out-of-plane views (IJV group) and the brachiocephalic vein with in-plane views (BCV group). The patients’ background characteristics, surgical outcomes, and complications were compared retrospectively.<i>Results</i>: A total of 40 tunneled CVCs (IJV group: n = 15, BCV group: n = 25) were inserted in 34 patients. The patients’ background characteristics were not significantly different between the two groups. The operative times were 30 min (range: 27–33 min) in the IJV group and 25.8 min (range: 22–27 min) in the BCV group. The BCV group had a significantly shorter operative time (p = 0.0026). Intraoperative complications were observed in one patient (6.7%) in the IJV group and none of the patients in the BCV group. Complications during maintenance were observed in 10 patients (66.7%) in the IJV group and 17 patients (68%) in the BCV group. Catheter-related bloodstream infection was noted in 10 patients (66.7%) in the IJV group and 12 patients (52%) in the BCV group; these infection rates were not significantly different. The periods of CVC implantation were 273 days (172–363.5 days) in the IJV group and 152 days (101–280 days) in the BCV group, which were not significantly different.<i>Conclusions</i>: A real-time US-guided supraclavicular approach to brachiocephalic catheterization was considered a safe technique for pediatric patients with hematological and oncological diseases.
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Matsumoto F, Yokogami K, Yamada A, Moritake H, Watanabe T, Yamashita S, Sato Y, Takeshima H
Human cell 37 ( 2 ) 523 - 530 2024.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Human Cell
Atypical teratoid/rhabdoid (AT/RT) is a rare and highly malignant tumor of the central nervous system (CNS). It is most commonly found in children less than 5 years of age and is associated with inactivation of loss of function of SMARCB1/INI1. An experimental model for AT/RT is necessary to develop new and effective therapies. We established a patient-derived new cell line (MZ611ATRT), which showed loss of BAF-47. MZ611ATRT genetically features somatic heterozygous deletion of SMARCB1 and single nucleotide deletion of the residual allele, exon 5 ([c.541delC]), resulting in a stop codon at codon 954 by frameshift. We assessed the RNA-sequencing data of the other two AT/RT cell lines with forced expression of SMARCB1 available from public databases. We found SMARCB1 overexpression significantly down-regulates the expression of a group of enzymes related to cholesterol biosynthesis. Simvastatin was highly sensitive against MZ611ATRT cells and induced apoptosis (IC50 was 3.098 µM for MZ611ATRT, 41.88uM for U-87 MG, 23.34uM for IOMM-Lee, and 18.12uM for U-251 MG.). Pathways involved in cholesterol biosynthesis may be new targets for adjuvant therapy of AT/RT.
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B-cell deficiency identified by newborn screening Reviewed
Matsumoto Takayuki, Nishimura Toyoki, Yamamoto Ayako, Sawada Hirotake, Moritake Hiroshi
JSIAD Journal 3 ( 1 ) 16 - 20 2024.2
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Society for Immunodeficiency and Autoinflammatory Diseases
Newborn screening（NBS）is carried out at public expense for approximately 20 diseases in Japan; however, each prefecture independently conducts additional NBS including several more diseases. Miyazaki Prefecture has optionally included inborn errors of immunity（IEIs）and lysosomal storage diseases since April 2020. We herein report a baby who suffered from B-cell deficiency（BCD）that was identified by NBS conducted in Miyazaki Prefecture. The baby had low levels of kappa-deleting recombination excision circles（KRECs）and was referred to our hospital. Several measurements of CD19-positive B cells in the peripheral blood consistently showed values <2%, leading to the diagnosis of BCD. Periodic immunoglobulin replacement successfully led to a healthy outcome without serious infection developing over a period of more than 17 months. This is the first case of BCD identified by NBS and that underwent prophylactic gamma globulin replacement in Japan. Severe combined immunodeficiency disease and BCD are IEIs known to cause severe sequelae, and patients sometimes die without a correct diagnosis being made; therefore, their early diagnosis and early treatment are extremely important. The inclusion of IEIs in NBS has proven to be cost-effective all over the world. In the future, it is expected that IEIs will be covered by NBS public funds in Japan as well.
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Ishimura M., Eguchi K., Sonoda M., Tanaka T., Shiraishi A., Sakai Y., Yasumi T., Miyamoto T., Voskoboinik I., Hashimoto K., Matsumoto S., Ozono S., Moritake H., Takada H., Ohga S.
International Journal of Hematology 119 ( 5 ) 592 - 602 2024
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Familial hemophagocytic lymphohistiocytosis (FHLH) is a fatal hyperinflammation syndrome arising from the genetic defect of perforin-mediated cytolysis. Curative hematopoietic cell transplantation (HCT) is needed before development of central nervous system (CNS) disease. We studied treatment outcomes of 13 patients (FHLH2 n = 11, FHLH3 n = 2) consecutively diagnosed from 2011 to 2022 by flow cytometric screening for non-myeloablative HCT in a regional treatment network in Kyushu, Japan. One patient with a novel PRF1 variant escaped screening, but all patients with FHLH2 reached diagnosis and 8 of them received HCT until 3 and 9 months of age, respectively. The earliest HCT was conducted 65 days after birth. Three pretransplant deaths occurred in newborns with liver failure at diagnosis. Ten posttransplant patients have remained disease-free, 7 of whom had no neurological involvement. Time from first etoposide infusion to HCT was shorter in patients without CNS disease or bleeding than in patients with those factors (median [range] days: 62 [50–81] vs. 122 [89–209], p = 0.016). Six of 9 unrelated patients had a PRF1 c.1090_1091delCT variant. These results suggest that the critical times to start etoposide and HCT are within 3 months after birth and during etoposide control, respectively. Newborn screening may increase the percentage of disease-free survivors without complications.
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Pediatric acute myeloid leukemia Reviewed
MORITAKE Hiroshi
Rinsho Ketsueki 65 ( 9 ) 928 - 936 2024
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
Acute myeloid leukemia (AML) accounts for approximately 25% of pediatric leukemia cases in Japan, with approximately 150 patients being newly diagnosed with AML annually. Pediatric acute myeloid leukemia is classified into three groups: myeloid leukemia associated with Down syndrome (ML-DS), acute promyelocytic leukemia (APL), and <i>de novo</i> AML. Patients with ML-DS have an event-free survival rate over 80%; however, relapsed patients have dismal outcomes, even if they receive hematopoietic cell transplantation. APL is curable with all-trans retinoic acid and arsenic trioxide. In <i>de novo</i> AML, 10% of patients fail to achieve remission, and approximately 30% of patients who successfully achieve remission subsequently experience AML relapse. This review highlights the therapeutic approach for these three diseases with context from past clinical studies in Japan, and shares promising new therapeutic options for relapsed/refractory <i>de novo</i> AML.
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Arima M., Inoue H., Misumi A., Tsukamoto S., Matsushita I., Araki S., Ohta M., Takahashi K., Imazato M., Goto T., Aoki Y., Tagawa K., Hirose M., Fujita Y., Yoshida N., Nakao S., Kondo H., Kusuhara K., Kimura K., Hasegawa S., Ikeda Y., Kodama Y., Moritake H., Ochiai M., Ohga S., Kishimoto J., Todaka K., Ieiri I., Sonoda K.H.
Japanese Journal of Ophthalmology 68 ( 5 ) 490 - 499 2024
Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Ophthalmology
Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). Study design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.
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Ebihara Shusei, Kodama Yoshihiko, Takamura Kazunari, Harada Masako, Moritake Hiroshi
Journal of Pediatric Cardiology and Cardiac Surgery advpub ( 0 ) 82 - 86 2024
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：特定非営利活動法人 日本小児循環器学会
Symptoms of coronavirus infectious disease 2019 (COVID-19) are usually mild in young patients. Some children, however, present with a significant degree of complications which may be associated with an excessive reaction by the immune system. Herein, we report an analysis of cytokine and chemokine in an 11-year-old girl diagnosed with left ventricular dysfunction and cardiac tamponade complicated with COVID-19. She recovered without complications after intravenous immunoglobulin, dexamethasone, remdesivir, and surgical pericardial drainage. Cytokine concentrations had markedly increased in the pericardial fluid specimen; especially for interleukin-6 being disproportionate to its serum concentration. Cytokine storm originating from the pericardial cavity was considered an underlying mechanism of her condition.
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Current status and future perspective of pediatric malignancy in Kyushu and Okinawa regions Reviewed
Moritake Hiroshi
The Japanese Journal of Pediatric Hematology / Oncology 61 ( 5 ) 318 - 323 2024
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Pediatric Hematology / Oncology
A pediatric malignancy is a representative “rare cancer”, with a yearly incidence of only 2,000. Therefore, it is reasonable to consolidate clinical expertise in “centers of excellence” where pediatric patients can be treated appropriately. Acute lymphoblastic leukemia is the most common pediatric malignancy, and there is little disparity in treatment outcomes between facilities because of the remarkable progress in treatment, making it a representative disease for which standardization is important. Thus, while consolidation is generally necessary for pediatric malignancies, standardization is particularly important in certain cases. In the Kyushu and Okinawa regions, cooperation between facilities in each prefecture and Kyushu University Hospital as a core hospital has been established. A facility can become a Japanese pediatric hematology and oncology specialist training facility via two routes: becoming an affiliate of Kyushu University Hospital or becoming an independent parent facility, for which certified instructors in pediatric hematology and oncology and certified surgeons for pediatric malignancies are required. Furthermore, a certain number of new patients with pediatric malignancy annually is necessary. There are only two independent facilities in the Kyushu and Okinawa regions, each able to discuss cases that are difficult to deal with and share information through monthly web conferencing systems. There are no difficulties in daily practice, although the successful training of certified instructors and surgeons is necessary to increase the number of independent facilities for the management of pediatric malignancies.
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Novel splice site variant of TMEM38B in osteogenesis imperfecta type XIV Reviewed
Kodama Y., Meiri S., Asada T., Matsuyama M., Makino S., Iwai M., Yamaguchi M., Moritake H.
Human Genome Variation 10 ( 1 ) 25 2023.12
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Human Genome Variation
Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by brittle bones. In this case report, we describe a patient who suffered from OI type XIV with a novel splice site variant in the TMEM38B gene. Further research is needed to better understand the relationship between the phenotype of OI type XIV and this variant.
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Outcomes following induction failure in Japanese children with acute lymphoblastic leukemia. Reviewed
Imai C, Sato A, Hiwatari M, Shimomura Y, Hori T, Suenobu S, Imamura T, Hara J, Hasegawa D, Takahashi H, Moriya K, Katayama S, Tomizawa D, Moritake H, Taga T, Horibe K, Koh K, Manabe A, Okamoto Y
International journal of hematology 118 ( 1 ) 99 - 106 2023.4
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
The characteristics and prognosis of Japanese children with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission after remission induction chemotherapy (i.e., experience induction failure) are poorly understood. Therefore, we retrospectively analyzed data of patients enrolled in Japanese clinical trials for newly diagnosed ALL between 1996 and 2009. Among 4956 participants, 89 (1.8%) experienced induction failure. With a 6.0-year median follow-up, the 5-year overall survival rate of the entire cohort was 43.0% ± 5.5%. Survival rates did not differ between patients with B-cell precursor ALL (BCP-ALL) and T-cell ALL (T-ALL). In multivariate analysis, day 15 M3 marrow (bone marrow blast count ≥ 25%) was significantly correlated with poorer survival in the whole or BCP-ALL cohorts. In T-ALL, age < 6 years was significantly associated with poor survival. However, due to the small sample size, this correlation must be further investigated. Most T-ALL and BCR-ABL-positive BCP-ALL patients underwent allogeneic stem cell transplantation (allo-SCT). Survival rates did not differ between BCR-ABL-negative BCP-ALL patients who did and did not undergo allo-SCT, possibly due to the inclusion of lower-risk patients in the latter group. In conclusion, the induction failure rate and survival after diagnosis of induction failure in our study were comparable to previously reported figures.
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BMPR2 variant may be related to pulmonary hypertension after lung irradiation Reviewed
Harada M., Yamada A., Nagasawa S., Yamashita N., Kinoshita M., Yoshiura K.i., Moritake H.
Pediatrics International 65 ( 1 ) e15652 2023.1
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Pediatrics International
DOI： 10.1111/ped.15652
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Pneumocystis pneumonia during everolimus therapy for Kasabach–Merritt phenomenon Reviewed
Otomi K., Yamada A., Kurogi J., Kamimura S., Moritake H.
Pediatrics International 65 ( 1 ) e15593 2023.1
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Pediatrics International
DOI： 10.1111/ped.15593
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NAGASAWA Shun, YAMADA Ai, KINOSHITA Mariko, KAMIMURA Sachiyo, TANAKA Hiroyuki, NISHIKAWA Takuro, OKAMOTO Yasuhiro, MORITAKE Hiroshi
Rinsho Ketsueki 64 ( 1 ) 23 - 29 2023
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
A 12-year-old girl developed Philadelphia chromosome-positive acute myeloid leukemia due to therapy-related myelodysplastic syndrome with monosomy 7 following neuroblastoma treatment. She underwent allogenic bone marrow transplantation from a human leukocyte antigens-DR1 locus-mismatched unrelated donor. However, on day 49 post transplantation, she presented with diarrhea due to gastrointestinal acute graft-versus-host disease (aGVHD), and treatments with prednisolone, budesonide rectal foam, and human mesenchymal stem cells were ineffective. Therefore, vedolizumab was administered from day 100, which improved the symptoms from gut stage 3 to gut stage 1. Consequently, prednisolone was withdrawn without any serious adverse effects. However, the symptoms worsened to gut stage 3 again; therefore, ruxolitinib was administered to achieve complete remission. Vedolizumab exhibits gut-selective action without systemic immunosuppressive activity. Hence, vedolizumab administration before other systemic immunosuppressive agents may be recommended in patients with steroid-refractory gastrointestinal aGVHD. Thus far, only a few reports have been published regarding the administration of vedolizumab and ruxolitinib for steroid-refractory gastrointestinal aGVHD in children. Further evidence should be obtained from patients treated with vedolizumab and ruxolitinib to confirm their effectiveness for pediatric steroid-refractory gastrointestinal aGVHD.
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Successful treatment of eltrombopag following immunosuppressive therapy in pediatric aplastic anemia Reviewed
KUBOTA Isamu, NAGASAWA Shun, NAKAGAWA Midori, YAMADA Ai, KINOSHITA Mariko, KAMIMURA Sachiyo, SHIMONODAN Hidemi, MORITAKE Hiroshi
Rinsho Ketsueki 64 ( 8 ) 741 - 745 2023
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
Immunosuppressive therapy (IST) is the first-line treatment for patients with aplastic anemia (AA) who require blood transfusion when a human leukocyte antigen-matched related donor is unavailable. However, the proportion of patients with AA who are refractory to IST remains high (30%). IST in combination with eltrombopag has been studied in adults, but its efficacy and safety in children have not been established. We present three cases of AA that were initially refractory to IST but improved with additional eltrombopag administration. These patients were successfully managed using this strategy without the use of hematopoietic cell transplantation (HCT). The first patient achieved a complete response within one month after receiving eltrombopag. When the second and third patients were given eltrombopag, they were able to safely reduce the amount of cyclosporin they were given. They avoided blood transfusions, but no measurable response was obtained. The conjunctival icterus was detected and treated using a dose reduction of eltrombopag. Eltrombopag may be effective in children with AA who are refractory to IST, allowing them to avoid blood transfusions and HCT. More cases treated with this strategy are needed to confirm its efficacy and safety for children with AA.
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Yamada A., Kinoshita M., Kamimura S., Jinnouchi T., Azuma M., Yamashita S., Yokogami K., Takeshima H., Moritake H.
Pediatric Hematology and Oncology 40 ( 7 ) 629 - 642 2023
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Pediatric Hematology and Oncology
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive central nervous system tumor that typically affects children under three years old and has poor survival with a high risk for neurologic deficits. The primary purpose of this study was to successfully treat the disease and delay or avoid whole-brain radiotherapy for children with AT/RT. A retrospective analysis was performed for six children diagnosed with AT/RT and treated with multimodal treatment at a single institute between 2014 and 2020. Furthermore, germline SMARCB1 aberrations and MGMT methylation status of the tumors were analyzed. One patient who did not receive a modified IRS-III regimen replaced with ifosphamide, carboplatin, and etoposide (ICE) in induction chemotherapy was excluded from this analysis. Five patients who received ICE therapy were under three years old. After a surgical approach, they received intensive chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) followed by intrathecal topotecan maintenance therapy. Three patients underwent single HDCT/autoPBSCT, and the other two received sequential treatment. Two patients with germline SMARCB1 aberrations and metastases died of progressive AT/RT or therapy-related malignancy, while 3 with localized tumors without germline SMARCB1 aberrations remained alive. One survivor received local radiotherapy only, while the other two did not undergo radiotherapy. All three surviving patients were able to avoid whole-brain radiotherapy. Our results suggest that AT/RT patients with localized tumors without germline SMARCB1 aberrations can be rescued with multimodal therapy, including induction therapy containing ICE followed by HDCT/autoPBSCT and intrathecal topotecan maintenance therapy without radiotherapy. Further large-scale studies are necessary to confirm this hypothesis.
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Tomizawa D., Matsubayashi J., Iwamoto S., Hiramatsu H., Hasegawa D., Moritake H., Hasegawa D., Terui K., Hama A., Tsujimoto S.i., Kiyokawa N., Miyachi H., Deguchi T., Hashii Y., Iijima-Yamashita Y., Taki T., Noguchi Y., Koike K., Koh K., Yuza Y., Moriya Saito A., Horibe K., Taga T., Tanaka S., Adachi S.
Leukemia 38 ( 1 ) 202 - 206 2023
Language：English Publishing type：Research paper (scientific journal) Publisher：Leukemia
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Left atrial appendage aneurysm enlarged in the neonatal period. Reviewed
Yamashita N, Harada M, Moritake H
Cardiology in the young 33 ( 8 ) 1 - 3 2022.12
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Cardiology in the Young
We describe a newborn with a congenital left atrial appendage aneurysm. The aneurysm size did not change prenatally. However, it rapidly enlarged after birth. MRI was useful for assessing the aneurysm extent and exact size, and for diagnosis. Respiratory distress and feeding difficulties appeared, and surgery was performed. These symptoms disappeared post-operatively. The patient is alive without complications or recurrence.
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パゾパニブが有効であった多発肺転移を有する難治性Ewing肉腫 Reviewed
2022.10
Authorship：Corresponding author Publishing type：Research paper (scientific journal)
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Yamada A., Kinoshita M., Kamimura S., Nakame K., Moritake H.
Journal of Pediatric Hematology/Oncology 44 ( 2 ) E589 - E592 2022.3
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Pediatric Hematology/Oncology
Neuroblastoma with bone metastasis is well known to have an extremely poor prognosis. We experienced the case of a patient with adrenal ganglioneuroblastoma (GNB) with metastases of subcutaneous nodules, a lymph node, and multiple bones. A pathologic examination of tumors from different sites revealed both GNB and ganglioneuroma. A genetic comparison between these tumors identified the same molecular signatures, suggesting the possibility of spontaneous differentiation in the remaining GNB. The patient has been healthy without aggressive chemotherapy, and the patient's pathologic urinary catecholamines normalized. Even if unusual, we have to recognize probable spontaneous differentiation from neuroblastoma to GNB and then to ganglioneuroma, even in sites of bone metastasis.
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A retrospective analysis of azacitidine treatment for juvenile myelomonocytic leukemia Reviewed
Honda Y., Muramatsu H., Nanjo Y., Hirabayashi S., Meguro T., Yoshida N., Kakuda H., Ozono S., Wakamatsu M., Moritake H., Yasui M., Sano H., Manabe A., Sakashita K.
International Journal of Hematology 115 ( 2 ) 263 - 268 2022.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Juvenile myelomonocytic leukemia (JMML) is a pediatric hematological malignancy with a poor prognosis. Although several case series have been published describing hematological and molecular responses to azacitidine (AZA) treatment in patients with JMML, the efficacy and safety profile of AZA is not well investigated, especially in Asian children and children undergoing hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 5 patients who received a total of 12 cycles (median 2 cycles) of AZA treatment in Japan. All five patients were boys and their ages at the time of treatment were 21, 23, 24, 26, and 46 months, respectively. All five patients tolerated AZA treatment, including four patients who received AZA after HSCT. Therapeutic toxicity with AZA was mostly limited to hematological toxicity. The only serious non-hematological adverse event was hyperbilirubinemia (grades III–IV) observed in a patient who received AZA after a second HSCT. Two out of five patients treated with AZA achieved a partial response (PR), while three patients treated for post-transplant relapse did not have an objective response. Future prospective studies should be conducted to develop combination therapies with AZA and other molecular targeted drugs for high-risk patients.
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Kinoshita M., Yamada A., Saito Y., Kamimura S., Moritake H.
Pediatrics international : official journal of the Japan Pediatric Society 64 ( 1 ) e14975 2022.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatrics international : official journal of the Japan Pediatric Society
DOI： 10.1111/ped.14975
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Nagasawa S., Yamada A., Kinoshita M., Kamimura S., Moritake H.
Pediatrics international : official journal of the Japan Pediatric Society 64 ( 1 ) e14970 2022.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatrics international : official journal of the Japan Pediatric Society
DOI： 10.1111/ped.14970
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Matsuyama Misayo, Sawada Hirotake, Inoue Shinobu, Hishinuma Akira, Sekiya Ryo, Sato Yuichiro, Moritake Hiroshi
Clinical Pediatric Endocrinology 31 ( 3 ) 185 - 191 2022
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society for Pediatric Endocrinology
<p>Thyroglobulin gene abnormalities cause thyroid dyshormonogenesis. A 6-yr-old boy of consanguineous parents presented with a large goiter and mild hypothyroidism (thyroid-stimulating hormone [TSH] 7.2 μIU/mL, free T3 [FT3] 3.4 pg/mL, free T4 [FT4] 0.6 ng/dL). Despite levothyroxine (LT4) administration and normal TSH levels, the goiter progressed slowly and increased rapidly in size at the onset of puberty. Thyroid scintigraphy revealed a remarkably high <sup>123</sup>I uptake of 75.2%, with a serum thyroglobulin level of 13 ng/ml, which was disproportionately low for the goiter size. DNA sequencing revealed a novel homozygous missense variant, c.434G>A [p.Gly145Glu], in the thyroglobulin gene. Goiter growth was suppressed by increasing the LT4 dose. Thyroidectomy was performed at 17-yr-of-age. Thyroglobulin analysis of the thyroid tissue detected mutant thyroglobulin present in the endoplasmic reticulum, demonstrating that thyroglobulin transport from the endoplasmic reticulum to the Golgi apparatus was impaired by the Gly145Glu variant. During the clinical course, an elevated FT3/FT4 ratio was observed along with thyroid enlargement. A high FT3/FT4 ratio and goiter seemed to be compensatory responses to impaired hormone synthesis. Thyroglobulin defects with goiter should be treated with LT4, even if TSH levels are normal.</p>
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集学的治療が有効であった顎下部原発滑膜肉腫 Reviewed
中川 緑,山田 愛,木下 真理子,齋藤 祐介,上村 幸代,石原 明,陣内 崇,楠原 和朗,小田 義直,盛武 浩
宮崎会医師会医学会誌 46 46 - 50 2022
Language：Japanese Publishing type：Research paper (scientific journal)
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妊娠中のポリフェノール含有飲食物の常習的摂取が原因と考えられた胎児動脈管早期収縮 Reviewed
楯真由美,黒木亜津子,山下 尚人,原田 雅子,盛武 浩
宮崎会医師会医学会誌 46 38 - 41 2022
Language：Japanese Publishing type：Research paper (scientific journal)
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ヒト脳脊髄液中topotecan濃度のHPLC分析法構築と髄腔内薬物投与後の排泄評価 Reviewed
吉川 直樹, 山田 愛, 横田 翼, 山田 侑世, 木下 真理子, 盛武 浩, 池田 龍二
日本臨床薬理学会学術総会抄録集 43 ( 0 ) 3-C-P-110 2022
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：一般社団法人 日本臨床薬理学会
【目的】抗悪性腫瘍薬の髄腔内投与は、髄液中の薬物濃度を高く維持し、全身性の副作用が最小化される利点を有する。しかし、脳室内薬物のクリアランスは全ての患者で一律ではない。従って、安全な抗悪性腫瘍薬の髄腔内投与のためには、局所薬物動態を評価可能な環境が必要である。髄腔内投与後の髄液中薬物濃度が評価できれば、患者ごとに適切な用法・用量での化学療法が可能となる。Topoisomerase I阻害剤topotecanは、横紋筋肉腫、髄芽腫、神経芽腫などの小児腫瘍の治療に使用され、その有効性が認識されてきている。髄腔内投与後の髄液中topotecan濃度の評価は第I相臨床試験に限定され、髄液中topotecan濃度モニタリングに基づく個別化医療については未だ議論されていない。そこで本研究では、HPLCを使用した簡便かつ再現性の高い髄液中topotecan濃度測定法を開発し、その臨床応用性を確認した。【方法】脳脊髄液中topotecan濃度を測定するためのHPLC法には、Prominence UFLCシステムおよびC18カラムを使用した。Topotecanは生理的条件下にてラクトン環が閉環したラクトン型と開環したカルボキシレート型が可逆的に平衡状態で存在する。本法では総topotecan濃度を定量するために、分析対象試料のラクトン環の状態をpH調整処理により制御した後、除蛋白処理を施した。Topotecanは蛍光検出により定量した（励起波長380 nm、発光波長520 nm）。さらに、topotecan髄腔内投与中の1歳児より脳脊髄液を採取し、本法にて脳脊髄液中topotecan濃度をモニタリングした。【結果・考察】脳脊髄液中topotecanは試料調製時のシンプルなpH調整により、閉環型および開環型への変換が確認された。この2形態は構築した分析法により明確に分離することができ、開環型と閉環型の保持時間はそれぞれ1.3分と3.2分であった。髄液が吸収不良により停滞する患者にトポテカンを髄腔内投与後、本法を用いて、投与24、48、72時間後の脳脊髄液中topotecan濃度をモニタリングした。投与24、48時間後において、投与量を反映した脳脊髄液中濃度の定量に成功した。従って本法は、髄腔内投与後のtopotecan排泄遅延を検出可能と考える。【結論】日常的なtopotecanモニタリングを実現することで、topotecanの髄腔内投与における投与量および投与間隔の適時調整が可能となった。本研究成果は、抗悪性腫瘍薬の髄腔内投与における個別化治療法の実現に貢献するものである。
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Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia Reviewed
Saito Y., Kinoshita M., Yamada A., Kawano S., Liu H.S., Kamimura S., Nakagawa M., Nagasawa S., Taguchi T., Yamada S., Moritake H.
Cancer Science 112 ( 12 ) 4944 - 4956 2021.12
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer Science
Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and the TCA cycle, therefore suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene-independent leukemia.
DOI： 10.1111/cas.15138
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Malignant perivascular epithelioid cell neoplasm in the liver: report of a pediatric case. Reviewed
Baba T, Kawano T, Saito Y, Onishi S, Yamada K, Yamada W, Masuya R, Nakame K, Kawasaki Y, Iino S, Sakoda M, Kirishima M, Kaji T, Tanimoto A, Natsugoe S, Ohtsuka T, Moritake H, Ieiri S
Surgical case reports 7 ( 1 ) 212 2021.9
Language：English Publishing type：Research paper (scientific journal)
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Taga T., Tanaka S., Hasegawa D., Terui K., Toki T., Iwamoto S., Hiramatsu H., Miyamura T., Hashii Y., Moritake H., Nakayama H., Takahashi H., Shimada A., Taki T., Ito E., Hama A., Ito M., Koh K., Hasegawa D., Saito A.M., Adachi S., Tomizawa D.
Leukemia 35 ( 9 ) 2508 - 2516 2021.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Leukemia
Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 95.0% and 96.7% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 98.1% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD with EFS were 14.67 (p = 0.01). Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.
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Yoshikawa N., Yamada A., Yokota T., Yamada Y., Kinoshita M., Moritake H., Ikeda R.
Cancers 13 ( 18 ) 2021.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancers
Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient’s topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.
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Azuma M., Kadota Y., Matsuyama M., Moritake H., Hirai T.
Japanese Journal of Radiology 39 ( 6 ) 564 - 570 2021.6
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Radiology
Objective: We evaluated the usefulness of fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) imaging for the evaluation of the ectopic posterior pituitary gland (EPPG). Materials and methods: This retrospective study included 9 patients with EPPG due to causes other than tumor. All underwent sagittal two-dimensional (2D) T1W-, FS 3D T1W-VISTA- (VISTA), and 3D T2W-driven equilibrium radiofrequency reset pulse (DRIVE) imaging. Two radiologists independently reviewed the 2D T1W- and VISTA images for their image quality and for visualization of the EPPG and of pituitary stalk transection. DRIVE findings were used as the reference standard for pituitary stalk transection. Interobserver and intermodality agreements were evaluated with the kappa (κ) coefficient. The mean grade assigned to the 2D T1W- and the VISTA imaging technique for visualization of the EPPG was assessed by the Mann–Whitney U test. Results: Interobserver agreement for visualization of the EPPG on 2D T1W- and VISTA images was excellent (κ = 0.82 and κ = 1.00, respectively). The mean grade for EPPG visualization was significantly higher for VISTA- than 2D T1W images (p = 0.0039). Conclusion: FS 3D T1W-VISTA imaging is useful for the evaluation of EPPG. A secondary abstract: Conventional MRI yields insufficient information for the evaluation of the ectopic posterior pituitary gland (EPPG). The visualization of the EPPG was significantly higher for fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) than 2D T1W images. FS 3D T1W-VISTA imaging is useful for the evaluation of the EPPG.
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Aoki T., Takahashi H., Tanaka S., Shiba N., Hasegawa D., Iwamoto S., Terui K., Moritake H., Nakayama H., Shimada A., Koh K., Goto H., Kosaka Y., Saito A.M., Horibe K., Kinoshita A., Tawa A., Taga T., Adachi S., Tomizawa D.
British Journal of Haematology 193 ( 1 ) 176 - 180 2021.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：British Journal of Haematology
The variability in myelosuppression after chemotherapy for acute myeloid leukaemia (AML) can affect its prognosis; however, the underlying mechanism remains controversial. In the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study, we showed that prolonged neutropenia was associated with high overall survival (P = 0·011) and low frequency of relapse (P = 0·042) in patients without granulocyte-colony stimulating factor (G-CSF) who completed the indicated treatment protocol. Our data indicate that predisposition to prolonged neutropenia after chemotherapy is correlated with a better outcome of AML treatment. Our results promote the usage of individualised drug dosing strategies to improve the therapeutic outcome in AML patients.
DOI： 10.1111/bjh.16656
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Yoshikawa N., Yamada A., Yokota T., Moritake H., Hirabara Y., Ikeda R.
Journal of Clinical Laboratory Analysis 35 ( 3 ) e23661 2021.3
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Clinical Laboratory Analysis
Background: The concentration of MTX in blood is often measured quickly and easily by immunoassays. Thus, immunoassays may facilitate the easy determination of the concentration of MTX in the cerebrospinal fluid (CSF). In this study, we measured methotrexate (MTX) concentrations in the CSF using a high-performance liquid chromatography (HPLC) method intended for analyzing CSF matrices and a chemiluminescence immunoassay (CLIA) method intended for assessing serum and plasma matrices and verified the differences in the results of the two methods. Methods: HPLC analysis for MTX in the CSF was performed using a Prominence UFLC system with a C18 column. The HPLC method was validated in accordance with the 2018 FDA guideline. The CLIA method was performed using an ARCHITECT i1000SR system intended for serum and plasma matrices. A total of 47 CSF samples (14 clinical and 33 spiked specimens) were analyzed using the two methods. Results: The HPLC method passed the validation criteria. The concentration of MTX in the same sample, determined using the HPLC and CLIA methods, differed proportionally; the percent difference in the concentrations averaged −23.0% (95% confidence interval: −36.9% to −9.1%) as revealed by the Bland-Altman plot. The relationship between the measured values, evaluated using the Passing-Bablok regression, was as follows: HPLC = 1.205 × CLIA – 0.024. Conclusion: The equation deduced in this study can be used to correct the concentration of MTX measured using the CLIA method.
DOI： 10.1002/jcla.23661
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A useful method to diagnose Pearson syndrome mimicking Diamond–Blackfan anemia Reviewed
Nishimura T., Yamada A., Utoyama M., Saito Y., Moritake H.
Pediatrics International 63 ( 2 ) 223 - 225 2021.2
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatrics International
DOI： 10.1111/ped.14385
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Moritake H., Tanaka S., Miyamura T., Nakayama H., Shiba N., Shimada A., Terui K., Yuza Y., Koh K., Goto H., Kakuda H., Saito A., Hasegawa D., Iwamoto S., Taga T., Adachi S., Tomizawa D.
Pediatric Blood and Cancer 68 ( 1 ) e28736 2021.1
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatric Blood and Cancer
Background: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation (HCT) as a second-line therapy and improvements in supportive care following anthracycline- and cytarabine-based chemotherapy; however, the outcomes of children with relapsed AML still remain unsatisfactory. Procedure: In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients who relapsed after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol and who were registered in the retrospective JPLSG AML-05R study. Results: The 5-year overall survival rate was 36.1%. The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the nonsurviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (P <.01). Moreover, achieving a second complete remission (CR2) prior to HCT was associated with a good prognosis (P <.01). Etoposide, cytarabine, and mitoxantrone (ECM)- or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (P <.01). A genetic analysis also revealed the prognostic significance of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication as a poor prognostic marker (P =.04) and core binding factor-AML, t(8;21), and inv(16) as good prognostic markers (P <.01). Conclusions: Achieving a CR2 prior to HCT is important in order to improve the prognosis of relapsed pediatric AML. Recent molecular targeted therapies, such as FLT3 inhibitors, may contribute to overcome their prognoses. Larger prospective investigations are necessary to establish individualized treatment strategies for patients with relapsed childhood AML.
DOI： 10.1002/pbc.28736
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Hasegawa D., Tawa A., Tomizawa D., Watanabe T., Saito A.M., Kudo K., Taga T., Iwamoto S., Shimada A., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Koh K., Goto H., Kosaka Y., Miyachi H., Horibe K., Nakahata T., Adachi S.
Pediatric Blood and Cancer 67 ( 12 ) e28692 2020.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatric Blood and Cancer
We previously reported that risk-stratified therapy and intensive postremission chemotherapy (PRC) contributed to the improved survival of childhood acute myeloid leukemia (AML) in the AML99 study, which led us to consider a reduction in the number of PRC courses with more restrictive indications for stem cell transplantation (SCT) in the successor AML-05 study. We here report the outcome of AML patients without core-binding factor mutation (non-CBF AML) in the AML-05 study. Two-hundred eighty-nine children (age < 18 years old) with non-CBF AML were eligible. Patients with unfavorable cytogenetics and/or poor bone marrow response to the first induction course were candidates for SCT in the AML-05 study. After two courses of induction, a further three courses of PRC were given in AML-05, while four courses were given in the AML99 study. The 3-year event-free survival (EFS) rate in the AML-05 study (46.7%, 95% CI: 40.6-52.6%) was comparable to that of non-CBF AML in the AML99 study (51.5%, 95% CI: 42.7-59.6%) (P =.16). However, the 3-year overall survival (OS) rate in the AML-05 study (62.9%, 95% CI: 56.3-68.8%) was slightly lower than that in the AML99 study (71.6%, 95% CI: 63.2-78.5%) (P =.060), mainly due to decreased remission induction rate and increased nonrelapsed mortality. In conclusion, reductions in the number of PRC courses from four to three, together with repetitive cycles of high-dose cytarabine, were acceptable for non-CBF childhood AML.
DOI： 10.1002/pbc.28692
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Prevention of cisplatin-induced hearing-loss by sodium thiosulfate in medulloblastoma Reviewed
Harao T, Yamada A, Kinoshita M, Kamimura S, Moritake H
62 ( 10 ) 1204 - 1206 2020.9
Authorship：Lead author, Last author Language：English Publishing type：Research paper (scientific journal)
DOI： 10.1111/ped.14271
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Temozolomide and etoposide combination for the treatment of relapsed osteosarcoma Reviewed
Akazawa R., Umeda K., Saida S., Kato I., Hiramatsu H., Sakamoto A., Arakawa Y., Sumiyoshi S., Okamoto T., Moritake H., Adachi S., Takita J.
Japanese Journal of Clinical Oncology 50 ( 8 ) 948 - 952 2020.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology
The prognosis of patients with relapsed osteosarcoma is extremely poor and the optimal treatment remains to be identified. Here, we retrospectively analysed the clinical outcomes of nine patients with relapsed osteosarcoma treated with temozolomide/etoposide. Of the two patients who received temozolomide/etoposide as palliative therapy for unresectable tumours, one remained alive with stable disease for >4 years. The remaining seven patients received temozolomide/etoposide as adjuvant therapy following resection of relapsed metastatic disease; of these, one was free from disease for 41 months. Potentially beneficial effects were observed in two of three O6-methylguanine-DNA methyltransferase protein-negative patients, whereas all five O6-methylguanine-DNA methyltransferase-positive patients experienced subsequent relapse. None of the patients experienced severe adverse effects requiring hospitalization. Temozolomide/etoposide is a feasible candidate as salvage therapy for relapsed osteosarcoma. Further studies are needed to verify the utility of O6-methylguanine-DNA methyltransferase protein expression as a biomarker for predicting the response to this treatment.
DOI： 10.1093/jjco/hyaa070
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Terui K., Toki T., Taga T., Iwamoto S., Miyamura T., Hasegawa D., Moritake H., Hama A., Nakashima K., Kanezaki R., Kudo K., Saito A.M., Horibe K., Adachi S., Tomizawa D., Ito E.
Genes Chromosomes and Cancer 59 ( 3 ) 160 - 167 2020.3
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Genes Chromosomes and Cancer
Myeloid leukemia associated with Down syndrome (ML-DS) is characterized by a predominance of acute megakaryoblastic leukemia, the presence of GATA1 mutations and a favorable outcome. Because DS children can also develop conventional acute myeloid leukemia with unfavorable outcome, detection of GATA1 mutations is important for diagnosis of ML-DS. However, myelofibrosis and the significant frequency of dry taps have hampered practical screening of GATA1 mutations using bone marrow (BM) samples. In response to those problems, 82 patients were enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-D11 study. GATA1 mutations were analyzed by Sanger sequencing (SS) using genomic DNA (gDNA) from BM and cDNA from peripheral blood (PB) followed by targeted next-generation sequencing (NGS) using pooled diagnostic samples. BM and PB samples were obtained from 71 (87%) and 82 (100%) patients, respectively. GATA1 mutations were detected in 46 (56%) and 58 (71%) patients by SS using BM gDNA and PB cDNA, respectively. Collectively, GATA1 mutations were identified in 73/82 (89%) patients by SS. Targeted NGS detected GATA1 mutations in 74/82 (90%) patients. Finally, combining the results of SS with those of targeted NGS, GATA1 mutations were identified in 80/82 (98%) patients. These results indicate that SS using BM gDNA and PB cDNA is a rapid and useful method for screening for GATA1 mutations in ML-DS patients. Thus, a combination of SS and targeted NGS is a sensitive and useful method to evaluate the actual incidence and clinical significance of GATA1 mutations in ML-DS patients.
DOI： 10.1002/gcc.22816
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Moritake Hiroshi
The Japanese Journal of Pediatric Hematology / Oncology 57 ( 3 ) 240 - 250 2020
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Pediatric Hematology / Oncology
Acute myeloid leukemia (AML) accounts for approximately 25% of pediatric leukemia cases, with approximately 180 patients newly diagnosed each year in Japan. In general, AML is classified into three groups [acute promyelocytic leukemia (APL), myeloid leukemia associated with Down syndrome (ML-DS), and others] and is treated with different treatment strategies. Retinoic acid with conventional chemotherapy leads to a safe and promising outcome in patients with APL. Recently, arsenic trioxide and gemtuzumab ozogamicin have been expected to reduce late complications and further improve treatment outcomes. Reduced-intensity chemotherapy is effective for patients with ML-DS; however, the prognoses of relapsed and refractory patients are dismal. Optimization of the classification of patients with ML-DS into several groups is desired; thus, the measurement of minimal residual disease by flow cytometry and the detection of <i>GATA1</i> mutations is expected. For patients with other types of AML, they may be further classified into three groups on the basis of risk stratification according to chromosome and genetic analyses and chemosensitivity to induction therapy. However, the prognosis of patients with a refractory or relapsed disease remains a serious problem that should be solved. A novel therapeutic approach that includes the use of FLT3 inhibitors, which has recently been approved in Japan for adult patients with relapsed and refractory AML bearing <i>FLT3</i>-ITD, will be necessary to improve their prognosis.
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MORITAKE Hiroshi
Rinsho Ketsueki 61 ( 6 ) 665 - 672 2020
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
In Japan, acute myeloid leukemia (AML) accounts for approximately 25% of all pediatric leukemias, with approximately 150 cases of newly diagnosed AML occurring annually. Approximately 10% of patients have primary induction failure and 30% of patients, who initially achieve remission in primary treatments, subsequently relapse. Novel treatment modalities need to be developed to further improve the prognosis of pediatric AML patients. AML is a heterogeneous genetic disease characterized by changes in the genome of hematopoietic progenitor cells. Recent studies that have made progress in research related to the pathogenesis of AML have suggested that genotype-specific treatment strategies are associated with increased efficacy. Potential new therapeutic alternatives for pediatric AML include: tyrosine kinase inhibitors, monoclonal or bispecific T-cell engager antibodies, chimeric antigen receptor T-cell therapy, and metabolic agents. This review highlights the current landscape of novel therapeutic approaches for childhood AML, including the results of both preclinical and clinical trials, as well as introducing the results of several preceding adult clinical studies, which could potentially be translated into pediatric AML patients.
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急速に片側腎の機能低下を認めたシスチン尿症の1例 Reviewed
黒木 純，此元 隆雄, 今村 秀明，中原 梢, 寺田 直樹, 上村 敏雄，賀本 敏行，盛武 浩
日本小児腎不全学会雑誌 40 297 - 300 2020
Authorship：Lead author, Last author Language：Japanese Publishing type：Research paper (scientific journal)
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乳幼児早期に経後腹膜到達法による腹腔鏡下腎摘出を行った片側多嚢胞性異形成腎の１例 Reviewed
長友 美佳, 此元 隆雄, 黒木 純, 今村 秀明, 中原 梢, 寺田 直樹, 上村 敏雄, 賀本 敏行, 盛武 浩
日本小児腎不全学会雑誌 40 301 - 304 2020
Authorship：Lead author, Last author Language：Japanese Publishing type：Case report
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乳児期早期に腎摘出を行った多嚢胞性異形成腎の1例 Reviewed
長友 美佳, 黒木 純, 今村 秀明, 此元 隆雄, 盛 武浩, 中原 梢, 寺田 直樹, 上村 敏雄, 賀本 敏行
日本小児腎臓病学会雑誌 32 ( 2 ) 157 - 158 2019.11
Publishing type：Case report
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Saito Y, Sawa D, Kinoshita M, Yamada A, Kamimura S, Suekane A, Ogoh H, Matsuo H, Adachi S, Taga T, Tomizawa D, Osato M, Soga T, Morishita K, Moritake H
Haematologica 105 ( 8 ) 2118 - 2129 2019.10
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Haematologica
Metabolic reprogramming of leukemia cells is important for survival, proliferation, and drug resistance under conditions of metabolic stress in the bone marrow. Deregulation of cellular metabolism, leading to development of leukemia, occurs through abnormally high expression of transcription factors such as MYC and Ecotropic Virus Integration site 1 protein homolog (EVI1). Overexpression of EVI1 in adults and children with mixed lineage leukemia-rearrangement acute myeloid leukemia (MLL-r AML) has a very poor prognosis. To identify a metabolic inhibitor for EVI1-induced metabolic reprogramming in MLL-r AML, we used an XFp extracellular flux analyzer to examine metabolic changes during leukemia development in mouse models of AML expressing MLL-AF9 and Evi1 (Evi1/MF9). Oxidative phosphorylation (OXPHOS) in Evi1/MF9 AML cells accelerated prior to activation of glycolysis, with a higher dependency on glutamine as an energy source. Furthermore, EVI1 played a role in glycolysis as well as driving production of metabolites in the tricarboxylic acid cycle. L-asparaginase (L-asp) exacerbated growth inhibition induced by glutamine starvation and suppressed OXPHOS and proliferation of Evi1/MF9 both in vitro and in vivo; high sensitivity to L-asp was caused by low expression of asparagine synthetase (ASNS) and L-asp-induced suppression of glutamine metabolism. In addition, samples from patients with EVI1+MF9 showed low ASNS expression, suggesting that it is a sensitive marker of L-asp treatment. Clarification of metabolic reprogramming in EVI1+ leukemia cells may aid development of treatments for EVI1+MF9 refractory leukemia.
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学童期に発症した腸重積症の1例 Reviewed
押方 真, 山下 尚人, 近藤 恭平, 盛武 浩, 鈴東 昌也
日本小児科学会雑誌 123 ( 10 ) 1586 - 1586 2019.10
Publishing type：Case report
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食道穿孔をきたしたリチウム電池誤飲
原尾 拓朗, 木許 恭宏, 盛武 浩, 鈴東 昌也, 井手 慎介
日本小児科学会雑誌 123 ( 10 ) 1586 - 1586 2019.10
Publishing type：Research paper (scientific journal)
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横紋筋融解を契機に判明したCPT2欠損症の兄弟例 Reviewed
宇藤山 麻衣子, 麻田 智子, 松山 美靜代, 盛武 浩, 澤田 浩武
日本小児科学会雑誌 123 ( 10 ) 1587 - 1587 2019.10
Publishing type：Case report
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インフルエンザ罹患を契機に顕在化した遅発型Leigh症候群の1例 Reviewed
横山 亮平 ,木許 恭宏, 谷口 英里奈, 池田 俊郎, 盛武 浩
日本小児科学会雑誌 123 ( 10 ) 1587 - 1587 2019.10
Publishing type：Case report
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胎児期発症拡張型心筋症の孤発例 Reviewed
押方 真, 山下 尚人, 近藤 恭平, 盛武 浩, 山口 智子, 紀 愛美, 山下 理絵, 児玉 由紀
日本小児科学会雑誌 123 ( 10 ) 1588 - 1588 2019.10
Publishing type：Research paper (scientific journal)
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超大量フェノバルビタールとケトン食療法に加えペランパネルが奏功したAERRPS Reviewed
黒木 亜津子, 木許 恭宏, 谷口 英里奈, 池田 俊郎, 盛武 浩
日本小児科学会雑誌 123 ( 10 ) 1588 - 1588 2019.10
Publishing type：Research paper (scientific journal)
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ヌシネルセンナトリウム髄腔内投与により呼吸・運動機能の改善を認めた脊髄性筋萎縮症I型 Reviewed
原尾 拓朗, 木許 恭宏, 谷口 英里奈, 池田 俊郎, 盛武 浩
日本小児科学会雑誌 123 ( 10 ) 1588 - 1589 2019.10
Publishing type：Research paper (scientific journal)
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HHV-6感染を契機とした急性壊死性脳症の1例 Reviewed
横山 亮平, 木許 恭宏, 谷口 英里奈, 池田 俊郎, 盛武 浩
日本小児科学会雑誌 123 ( 10 ) 1589 - 1589 2019.10
Publishing type：Case report
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リツキシマブ投与を行った難治性ネフローゼ症候群の検討 Reviewed
黒木 純, 今村 秀明, 此元 隆雄, 盛武 浩
日本小児科学会雑誌 123 ( 10 ) 1589 - 1589 2019.10
Publishing type：Research paper (scientific journal)
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JPLSGにおける急性骨髄性白血病治療の歴史と現状、そして克服すべき課題について Reviewed
盛武 浩
日本小児血液・がん学会雑誌 56 ( 4 ) 171 - 171 2019.10
Publishing type：Research paper (scientific journal)
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チオ硫酸ナトリウム使用によりシスプラチン誘発性聴力障害の進行が抑制された髄芽腫 Reviewed
原尾 拓朗, 山田 愛, 木下 真理子, 齋藤 祐介, 上村 幸代, 盛武 浩
日本小児血液・がん学会雑誌 56 ( 4 ) 341 - 341 2019.10
Publishing type：Research paper (scientific journal)
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市中型MRSA敗血症を併発した細菌性気管炎の1例 Reviewed
原田 雅子, 入佐 浩史, 黒木 純, 山下 尚人, 山元 綾子, 木許 恭宏, 今村 秀明, 盛武 浩, 宮原 史和
日本小児呼吸器学会雑誌 30 126 - 126 2019.9
Publishing type：Case report
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抗MOG抗体陽性のtumefactive demyelinating lesion(TDL)の1例 Reviewed
木許 恭宏, 原尾 拓朗, 谷口 英里奈, 池田 俊郎, 盛武 浩
脳と発達 51 ( 5 ) 332 - 332 2019.9
Publishing type：Case report
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パゾパニブで延命効果を認めた難治性Ewing肉腫 Reviewed
横山 亮平, 山田 愛, 木下 真理子, 澤 大介, 齋藤 祐介, 上村 幸代, 盛武 浩
日本小児血液・がん学会雑誌 56 ( 2 ) 272 - 272 2019.9
Publishing type：Research paper (scientific journal)
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小児悪性肝Perivascular epithelioid cell tumorの1例 Reviewed
村上 雅一, 馬場 徳朗, 中目 和彦, 向井 基, 加治 建, 家入 里志, 児玉 祐一, 河野 嘉文, 齋藤 祐介, 盛武 浩
日本小児血液・がん学会雑誌 56 ( 2 ) 274 - 274 2019.9
Publishing type：Case report
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BTNL2 germline variants may be involved in the pathogenesis of renal granuloma Reviewed International journal
Nishimura T, Yamada A, Kinoshita M, Ohara O, Moritake H.
Pediatr Int 61 ( 8 ) 834 - 836 2019.8
Authorship：Lead author, Last author Language：English Publishing type：Research paper (scientific journal)
DOI： 10.1111/ped.13923
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Long-term Remission of Acute Myeloid Leukemia Developed From Systemic Mastocytosis by Conventional Chemotherapy. Reviewed
Yamada A, Kinoshita M, Sawa D, Saito Y, Kamimura S, Miyachi H, Moritake H
Journal of pediatric hematology/oncology 2019.8
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal)
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Ochiai K., Yamada A., Kimoto Y., Imamura H., Ikeda T., Matsukubo M., Ieiri S., Moritake H.
Pediatric Blood and Cancer 66 ( 8 ) e27804 2019.8
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatric Blood and Cancer
© 2019 Wiley Periodicals, Inc. We report a 38-month-old Japanese male with premature chromatid separation/mosaic variegated aneuploidy syndrome bearing biallelic BUB1B germline mutations who suffered from bilateral Wilms tumor. After right nephrectomy, dactinomycin monotherapy was administered for the left Wilms tumor; however, severe adverse reaction prevented the patient from receiving further chemotherapy. Left nephrectomy was then performed without postoperative chemotherapy. The patient survived for 15 months after bilateral nephrectomy without peritoneal relapse, metastasis of Wilms tumor, or the occurrence of rhabdomyosarcoma and maintained a good quality of life while receiving peritoneal dialysis at home.
DOI： 10.1002/pbc.27804
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嘔吐恐怖から回避・制限性食物摂取症を合併した自閉スペクトラム症 Reviewed
長尾 愛美, 松山 美靜代, 盛武 浩
日本認知・行動療法学会大会プログラム・抄録集 2019.8
Publishing type：Research paper (conference, symposium, etc.)
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Okumura T., Horie Y., Lai C., Lin H., Shoda H., Natsumoto B., Fujio K., Kumaki E., Okano T., Ono S., Tanita K., Morio T., Kanegane H., Hasegawa H., Mizoguchi F., Kawahata K., Kohsaka H., Moritake H., Nunoi H., Waki H., Tamaru S., Sasako T., Yamauchi T., Kadowaki T., Tanaka H., Kitanaka S., Nishimura K., Ohtaka M., Nakanishi M., Otsu M.
Stem Cell Research and Therapy 10 ( 1 ) 185 2019.6
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Stem Cell Research and Therapy
© 2019 The Author(s). Background: Disease modeling with patient-derived induced pluripotent stem cells (iPSCs) is a powerful tool for elucidating the mechanisms underlying disease pathogenesis and developing safe and effective treatments. Patient peripheral blood (PB) cells are used for iPSC generation in many cases since they can be collected with minimum invasiveness. To derive iPSCs that lack immunoreceptor gene rearrangements, hematopoietic stem and progenitor cells (HSPCs) are often targeted as the reprogramming source. However, the current protocols generally require HSPC mobilization and/or ex vivo expansion owing to their sparsity at the steady state and low reprogramming efficiencies, making the overall procedure costly, laborious, and time-consuming. Methods: We have established a highly efficient method for generating iPSCs from non-mobilized PB-derived CD34+ HSPCs. The source PB mononuclear cells were obtained from 1 healthy donor and 15 patients and were kept frozen until the scheduled iPSC generation. CD34+ HSPC enrichment was done using immunomagnetic beads, with no ex vivo expansion culture. To reprogram the CD34+-rich cells to pluripotency, the Sendai virus vector SeVdp-302L was used to transfer four transcription factors: KLF4, OCT4, SOX2, and c-MYC. In this iPSC generation series, the reprogramming efficiencies, success rates of iPSC line establishment, and progression time were recorded. After generating the iPSC frozen stocks, the cell recovery and their residual transgenes, karyotypes, T cell receptor gene rearrangement, pluripotency markers, and differentiation capability were examined. Results: We succeeded in establishing 223 iPSC lines with high reprogramming efficiencies from 15 patients with 8 different disease types. Our method allowed the rapid appearance of primary colonies (~ 8 days), all of which were expandable under feeder-free conditions, enabling robust establishment steps with less workload. After thawing, the established iPSC lines were verified to be pluripotency marker-positive and of non-T cell origin. A majority of the iPSC lines were confirmed to be transgene-free, with normal karyotypes. Their trilineage differentiation capability was also verified in a defined in vitro assay. Conclusion: This robust and highly efficient method enables the rapid and cost-effective establishment of transgene-free iPSC lines from a small volume of PB, thus facilitating the biobanking of patient-derived iPSCs and their use for the modeling of various diseases.
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当科で経験した難治頻回部分発作重積型急性脳炎(AERRPS)の3例 Reviewed
木許 恭宏, 谷口 英里奈, 唐澤 直希, 中原 彰彦, 池田 俊郎, 盛武 浩
脳と発達 51 S388 - S388 2019.5
Publishing type：Case report
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小児悪性肝Perivascular epithelioid cell tumorの1例 Reviewed
長野 綾香, 馬場 徳朗, 川野 孝文, 村上 雅一, 矢野 圭輔, 大西 峻, 春松 敏夫, 山田 和歌, 山田 耕嗣, 桝屋 隆太, 町頭 成郎, 中目 和彦, 向井 基, 加治 建, 家入 里志, 児玉 祐一, 河野 嘉文, 斎藤 祐介, 盛武 浩
日本小児外科学会雑誌 55 ( 3 ) 759 - 759 2019.5
Publishing type：Research paper (scientific journal)
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RAS関連自己免疫性リンパ増殖症候群様疾患(RALD)に対する造血細胞移植 Reviewed
江口 克秀, 石村 匡崇, 小野 宏彰, 長谷川 一太, 園田 素史, 白石 暁, 古賀 友紀, 盛武 浩, 高田 英俊, 大賀 正一
臨床血液 60 ( 5 ) 489 - 490 2019.5
Publishing type：Research paper (scientific journal)
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造血幹細胞移植後に急性白質脳症を示した1例 Reviewed
川上 沙織, 辻 百衣璃, 山田 愛, 小野 宏彰, 一宮 優子, 賀来 典之, 石崎 義人, 實藤 雅文, 大場 詩子, 古賀 友紀, 酒井 康成, 盛武 浩, 大賀 正一
脳と発達 51 S338 - S338 2019.5
Publishing type：Case report
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Clinical and biological features of paediatric acute myeloid leukaemia (AML) with primary induction failure in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study. Reviewed
Miyamura T, Moritake H, Nakayama H, Tanaka S, Tomizawa D, Shiba N, Saito AM, Tawa A, Shimada A, Iwamoto S, Hayashi Y, Koike T, Horibe K, Manabe A, Mizutani S, Taga T, Adachi S
British journal of haematology 2019.2
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Saito A., Nishikawa T., Oyoshi T., Nakagawa S., Kodama Y., Yamada A., Kinoshita M., Okamoto Y., Arita K., Moritake H., Kawano Y.
Bone Marrow Transplantation 54 ( 2 ) 312 - 315 2019.2
Language：English Publishing type：Research paper (scientific journal)
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KIT変異陽性全身性肥満細胞症から進展し異なる転帰を呈した急性骨髄性白血病の2例 Reviewed
山田 愛, 木下 真理子, 澤 大介, 齋藤 祐介, 上村 幸代, 宮地 勇人, 荻野 尚, 児玉 祐一, 河野 嘉文, 盛武 浩
日本小児科学会雑誌 123 ( 2 ) 319 - 319 2019.2
Publishing type：Case report
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新生児期に拡大を認めた巨大左心耳瘤の1例 Reviewed
山下 尚人), 近藤 恭平, 原田 雅子, 盛武 浩, 豊村 大亮, 鈴木 彩代, 鍋島 泰典, 寺師 英子, 倉岡 彩子, 兒玉 祥彦, 石川 友一, 中村 真, 佐川 浩一, 石川 司朗
日本小児科学会雑誌 123 ( 2 ) 365 - 365 2019.2
Publishing type：Case report
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3D mock-up to guide intrathecal drug administration to address SMA and scoliosis Reviewed
123 ( 2 ) 366 - 366 2019.2
Publishing type：Research paper (scientific journal)
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超大量フェノバルビタールとケトン食療法に加えペランパネルが奏功したAERRPS Reviewed
黒木 亜津子, 谷口 英里奈, 木許 恭宏, 池田 俊郎, 盛武 浩
日本小児科学会雑誌 123 ( 2 ) 416 - 416 2019.2
Publishing type：Research paper (scientific journal)
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赤芽球癆所見を示しミトコンドリアDNA欠失により診断したPearson症候群 Reviewed
西村 豊樹, 山田 愛, 木下 真理子, 澤 大介, 齋藤 祐介, 上村 幸代, 盛武 浩
日本小児科学会雑誌 123 ( 2 ) 491 - 491 2019.2
Publishing type：Research paper (scientific journal)
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パゾパニブが有効であった多発肺転移を有する難治性Ewing肉腫 Reviewed
横山 亮平, 山田 愛, 木下 真理子, 澤 大介, 齋藤 祐介, 上村 幸代, 盛武 浩
日本小児科学会雑誌 123 ( 2 ) 494 - 494 2019.2
Publishing type：Research paper (scientific journal)
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Dextromethorphan内服治療を行ったメトトレキサート脳症の1例 Reviewed
木許 恭宏, 谷口 英里奈, 池田 俊郎, 盛武 浩
脳と発達 51 ( 1 ) 42 - 42 2019.1
Publishing type：Case report
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HARAO Takuro, OKAMOTO Yasuhiro, KAWANO Yoshifumi, MORITAKE Hiroshi, YAMADA Ai, KINOSHITA Mariko, SAWA Daisuke, SAITO Yusuke, KAMIMURA Sachiyo, MIYACHI Hayato, OGINO Takashi, KODAMA Yuichi
Rinsho Ketsueki 60 ( 5 ) 378 - 381 2019
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
Here, we report the case of a 9-year-old girl with acute myeloid leukemia (AML) developed from systemic mastocytosis (SM). She experienced bladder and rectal disturbance due to an extramedullary nodule in the paraspinal region of the sacrum. Cytogenetic and genetic analyses of leukemic cells revealed the <i>KIT</i> D816Y mutation besides t (8;21) (q22:q22) /<i>RUNX1</i>-<i>RUNX1T1</i>. Despite receiving proton beam therapy after conventional chemotherapy, the patient relapsed after 2 months. As SM-AML with the <i>KIT</i> D816 mutation in adults exhibits a poor prognosis, hematopoietic stem cell transplantation is recommended. Owing to a few reports of SM-AML in children, the standard therapy for pediatric cases has not been established to date. Based on our experience and the related literature, the prognosis of childhood SM-AML could be as poor as in adults. Hence, further investigation, including mutational analyses of the <i>KIT</i> gene, is warranted to establish a risk-oriented strategy for managing childhood SM-AML.
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KIT D816 変異陽性全身性肥満細胞症から進展し化学療法終了後2 ヶ月で再発した急性骨髄性白血病 Reviewed
原尾拓朗,山田愛,木下真理子, 澤大 介,齋藤祐介,上村幸代,宮地勇人,荻野尚，児玉祐一,岡本康裕，河野嘉文， 盛武浩
臨床血液 60 ( 5 ) 378 - 381 2019
Language：Japanese Publishing type：Research paper (scientific journal)
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呼吸不全が先行した急性弛緩性脊髄炎の幼児例 Reviewed
池田 俊郎,黒木亜津子, 木許 恭宏,谷口英里奈,盛武浩
宮崎県医師会医学会誌 42 ( 1 ) 60 - 64 2019
Language：Japanese Publishing type：Research paper (scientific journal)
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進行神経芽腫の再発との鑑別が困難であった限局性結節性過形成の2例 Reviewed
落合佳代，山田 愛，木下真理子，澤 大介，齋藤祐介，上村幸代，佐藤勇一郎，西川拓朗，岡本康裕，河野嘉文，川野正人，川野孝文，家入里志，盛武 浩
日本小児科学会雑誌 123 ( 9 ) 1400 - 1405 2019
Authorship：Lead author, Last author Language：Japanese Publishing type：Case report
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生体腎移植後の移植腎尿管結石反復例 Reviewed
山元綾子，今村秀明，此元隆雄，上村敏雄，賀本敏行，石塚喜世伸，服部元史，清水朋一，石田英樹，田邉一成，盛武 浩
日本小児腎不全学会雑誌 39 180 - 183 2019
Authorship：Lead author, Last author Language：Japanese Publishing type：Research paper (scientific journal)
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新生児けいれんを契機に診断された家族歴のない血友病の1例 Reviewed
河野猛嗣、児玉由紀、山下理絵、紀愛美、椎葉望、金子政時、鮫島浩、松澤聡史、大橋昌尚、堂福美佳、山田愛、木下真理子、上村幸代、盛武浩
宮崎県医師会医学会誌 42 ( 2 ) 163 - 168 2018.12
Language：Japanese Publishing type：Case report
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血清学的異常所見やSLE臨床所見に乏しいループス腎炎疑い例 Reviewed
黒木 純, 今村 秀明, 阪口 嘉美, 此元 隆雄, 盛 武浩, 久野 敏
日本小児腎臓病学会雑誌 31 ( 2 ) 203 - 203 2018.11
Publishing type：Case report
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KIT D816変異陽性全身性肥満細胞症から進展し傍脊髄髄外病変に陽子線治療を施行した急性骨髄性白血病 Reviewed
原尾拓朗、山田愛、木下 真理子、澤大介、齋藤祐介、上村幸代、宮地勇人、萩野尚、盛武浩
日本小児血液・がん学会雑誌 55 ( 4 ) 314 - 314 2018.10
Publishing type：Research paper (scientific journal)
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Adalimumab for treatment of hemophagocytic syndrome following unrelated bone marrow transplantation in a boy with Behcet's disease and secondary myelodysplastic syndrome Reviewed International journal
Noguchi M, Moritake H, Kamimura S, Sonoda M, Ishimura M, Inagaki J
Bone Marrow Transplant 53 ( 9 ) 1214 - 1217 2018.9
Language：English Publishing type：Research paper (scientific journal)
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横紋筋融解を契機に判明したCPT2欠損症の兄弟例 Reviewed
麻田 智子, 宇藤山 麻衣子, 松山 美靜代, 盛武 浩, 澤田 浩武, 原 圭一, 但馬 剛
日本先天代謝異常学会雑誌 34 214 - 214 2018.9
Publishing type：Case report
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EVI1 confers to the metabolic reprograming associated with leukemogenesis Reviewed
59 ( 9 ) 1507 - 1507 2018.9
Publishing type：Research paper (scientific journal)
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軽症溶血性尿毒症症候群後に紫斑病性腎炎を発症した児の腎病理像 Reviewed
黒木 純, 今村 秀明, 阪口 嘉美, 田中 悦子, 織田 真悠子, 此元 隆雄, 久野 敏, 盛武 浩
日本小児腎不全学会雑誌 38 214 - 216 2018.7
Language：Japanese Publishing type：Research paper (scientific journal)
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PLCE1遺伝子変異を認めた巣状分節性糸球体硬化症の1歳児例 Reviewed
下田 貴史, 今村 秀明, 此元 隆雄, 中西 啓太, 野津 寛大, 飯島 一誠, 阪口 嘉美, 久野 敏, 盛武 浩
日本小児腎不全学会雑誌 38 197 - 200 2018.7
Language：Japanese Publishing type：Case report
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Shimada A., Iijima-Yamashita Y., Tawa A., Tomizawa D., Yamada M., Norio S., Watanabe T., Taga T., Iwamoto S., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Koh K., Goto H., Kosaka Y., Saito A., Kiyokawa N., Horibe K., Hara Y., Oki K., Hayashi Y., Tanaka S., Adachi S.
International Journal of Hematology 107 ( 5 ) 586 - 595 2018.5
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
© 2018, The Japanese Society of Hematology. Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AMLFLT3-ITD) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AMLFLT3-ITD patients were assigned to receive hematopoietic stem cell transplantation (HSCT) in the first remission (1CR). We also investigated the effects of additional genetic alterations on FLT3-ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among the 47 AMLFLT3-ITD patients were 42.2 and 36.8%, respectively. The 5-year disease-free survival rate among 29 patients without induction failure was 58.4%. We defined the allelic ratio (AR) of FLT3-ITD to WT > 0.7 as high. Significant differences were found in OS (AR-high, 20% vs. AR-low, 66%, p < 0.001) and EFS (13 vs. 50%, p = 0.004). All five patients with concurrent NPM1 mutations survived, while seven of eight patients who expressed the NUP98-NSD1 chimera failed to achieve 1CR and died. Multivariate analysis revealed that AR > 0.7 and expression of the NUP98-NSD1 chimera strongly impacted OS and EFS. Although all the AMLFLT3-ITD patients received HSCT at 1CR, the treatment outcome of AMLFLT3-ITD patients did not improve compared with those in a previous study. Heterogeneity was observed among AMLFLT3-ITD patients.
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代理ミュンヒハウゼン症候群による食塩中毒が疑われた重症心身障害者例 Reviewed
高村 一成, 今村 秀明, 谷口 英里奈, 木許 恭宏, 池田 俊郎, 此元 隆雄, 日高 倫子, 大山 龍介, 盛武 浩
日本小児体液研究会誌 10 39 - 43 2018.5
Language：Japanese Publishing type：Research paper (scientific journal)
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Diagnosis of pediatric neuroblastoma by urine cytology: A case report. Reviewed
Nishikawa S., Noguchi H., Tokumitsu T., Ohno A., Moriguchi-Goto S., Maekawa K., Asada Y., Moritake H., Kinoshita M., Yamada A., Takamura K., Sato Y.
Diagnostic cytopathology 46 ( 3 ) 280 - 283 2018.3
Language：English Publishing type：Research paper (scientific journal)
DOI： 10.1002/dc.23831
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Kinoshita M., Yamada A., Sawa D., Kamimura S., Miyachi M., Moritake H.
Pediatric Blood and Cancer 65 e26750 2018.1
Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatric Blood and Cancer
© 2017 Wiley Periodicals, Inc. A 3-year-old male presented with a large retroperitoneal mass and multiple metastases. Biopsy results suggested alveolar rhabdomyosarcoma bearing a methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. Serum microRNA-206 levels were elevated and remained high after three cycles of vincristine, dactinomycin, and cyclophosphamide (VAC). Replacement of vincristine, irinotecan, and temozolomide (VIT) for VAC induced a marked tumor reduction and normalization of the miR-206 levels. The patient completed 14 cycles of VIT with local radiotherapy and has been in remission for 31 months. Temozolomide could be effective for tumors with a methylated MGMT gene promoter. Individualized therapy is warranted for such patients.
DOI： 10.1002/pbc.26750
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Diagnosis, surveillance, and management of familial leukemia Reviewed
MORITAKE Hiroshi
Rinsho Ketsueki 59 ( 10 ) 2290 - 2299 2018
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
Recently, the modern technique of comprehensive genomic analysis has identified both somatic mutations originating from tumor cells and germline mutations as causative genes of inherited familial leukemias among which Fanconi anemia and Li-Fraumeni syndrome are well known. Pathogenic germline mutations occur in various pathways, affecting DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, neutrophil development, and other critical cellular processes. The clinical manifestations of germline mutations present a wide phenotypic spectrum of patients displaying congenital anomalies, early-onset myelodysplastic syndrome, or no medical problems until the developing leukemia. The use of genetic tests to identify these affected persons will significantly benefit cancer surveillance and subsequent therapeutic interventions. Although familial leukemia treatment usually focuses on children, it is important for clinicians to recognize that familial leukemias can occur at any age, even among older adults. Genetic counseling after diagnosis is essential, and an immediate referral to experts in each disease is recommended.
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小児急性リンパ性白血病のvery late relapse例の予後 九州・山口小児がん治療研究グループ(KYCCSG)ALL 96/02研究 Reviewed
野口 磨依子, 稲垣 二郎, 岡本 康裕, 古賀 友紀, 大園 秀一, 新小田 雄一, 中山 秀樹, 盛武 浩, 堀田 紀子, 糸長 伸能, 野村 優子, 下之段 秀美, 市村 卓也, 日高 靖文, 河野 嘉文
日本小児血液・がん学会雑 54 ( 5 ) 393 - 397 2018
Language：Japanese Publishing type：Research paper (scientific journal)
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けいれん重積型急性脳症と鑑別を要した乳児揺さぶり症候群の１例 Reviewed
服部 洋平,門田 善仁,東 美菜子,陣内 崇,盛武 浩,平井 俊範
宮崎県医師会医学会誌 42 207 - 211 2018
Language：Japanese Publishing type：Case report
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Nakayama H., Tomizawa D., Tanaka S., Iwamoto S., Shimada A., Saito A., Yamashita Y., Moritake H., Terui K., Taga T., Matsuo H., Kosaka Y., Koh K., Hosoi H., Kurosawa H., Isoyama K., Horibe K., Mizutani S., Adachi S.
Pediatrics International 59 1046 - 1052 2017.10
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatrics International
© 2017 Japan Pediatric Society Background: The combination of fludarabine (Flu), high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF; FLAG), with anthracyclines has become standard chemotherapy for refractory acute myeloid leukemia (AML) in European children and adults. To clarify the efficacy and the safety of FLAG-idarubicin (IDA) for children prospectively, we planned a multicenter phase II study (AML-R11) by the Japanese Pediatric Leukemia/Lymphoma Study Group. Methods: Patients with AML aged between 2 and 20 years old, who had the first bone marrow (BM) relapse or induction failure, were enrolled. The FLAG-IDA regimen consisted of Flu 30 mg/m 2 for 5 days, Ara-C 2 g/m 2 for 5 days, G-CSF (lenograstim) 5 μg/kg for 6 days and IDA 10 mg/m 2 for 3 days. The primary endpoint was remission rate after therapy. Results: Due to drug supply issues, the trial was suspended after the inclusion of seven eligible patients. There were six cases of early relapse within 1 year of the first remission. All seven patients completed the therapy and no early death was observed. Hematological toxicity was common, and one patient developed grade 4 non-hematological toxicity of bacterial meningitis. Although only one patient with late relapse achieved complete remission, minimal residual disease was positive on both flow cytometry and Wilms’ tumor 1 mRNA. Two patients were alive in remission following hematopoietic stem cell transplantation, whereas the other five patients died of either the disease or treatment-related causes. Conclusion: FLAG-IDA might be tolerable for children with refractory AML although the efficacy should be further investigated.
DOI： 10.1111/ped.13378
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自家末梢血幹細胞移植後の血栓性微小血管障害にエクリズマブが著効した神経芽腫症例 Reviewed
山田 愛, 盛武 浩, 木下 真理子, 澤 大介, 今村 秀明, 上村 幸代, 此元 隆雄, 布井 博幸
日本小児科学会雑誌 121 ( 10 ) 1712 - 1718 2017.10
Language：Japanese Publishing type：Research paper (scientific journal)
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Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia Reviewed
Seki M., Kimura S., Isobe T., Yoshida K., Ueno H., Nakajima-Takagi Y., Wang C., Lin L., Kon A., Suzuki H., Shiozawa Y., Kataoka K., Fujii Y., Shiraishi Y., Chiba K., Tanaka H., Shimamura T., Masuda K., Kawamoto H., Ohki K., Kato M., Arakawa Y., Koh K., Hanada R., Moritake H., Akiyama M., Kobayashi R., Deguchi T., Hashii Y., Imamura T., Sato A., Kiyokawa N., Oka A., Hayashi Y., Takagi M., Manabe A., Ohara A., Horibe K., Sanada M., Iwama A., Mano H., Miyano S., Ogawa S., Takita J.
Nature Genetics 49 1274 - 1281 2017.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Nature Genetics
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved. The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric T-ALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), accounting for 3.9% (7/181) of the examined pediatric T-ALL cases, showed a double-negative (DN; CD4 - CD8 -) or CD8 + single-positive (SP) phenotype and had uniformly poor overall survival. These cases represent a subset of pediatric T-ALL distinguishable from the known T-ALL subsets in terms of expression of genes involved in T cell precommitment, establishment of T cell identity, and post-β-selection maturation and with respect to mutational profile. PU.1 fusion proteins retained transcriptional activity and, when constitutively expressed in mouse stem/progenitor cells, induced cell proliferation and resulted in a maturation block. Our findings highlight a unique role of SPI1 fusions in high-risk pediatric T-ALL.
DOI： 10.1038/ng.3900
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Yamato G., Shiba N., Yoshida K., Shiraishi Y., Hara Y., Ohki K., Okubo J., Okuno H., Chiba K., Tanaka H., Kinoshita A., Moritake H., Kiyokawa N., Tomizawa D., Park M., Sotomatsu M., Taga T., Adachi S., Tawa A., Horibe K., Arakawa H., Miyano S., Ogawa S., Hayashi Y.
Genes Chromosomes and Cancer 56 ( 5 ) 382 - 393 2017.5
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Genes Chromosomes and Cancer
© 2017 Wiley Periodicals, Inc. ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0–17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event-free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild-type (5-year OS, 75% vs. 100% vs. 91% and 5-year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously.
DOI： 10.1002/gcc.22443
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Ikeda T., Nakahara A., Nagano R., Utoyama M., Obara M., Moritake H., Uechi T., Mitsui J., Ishiura H., Yoshimura J., Doi K., Kenmochi N., Morishita S., Nishino I., Tsuji S., Nunoi H.
Journal of Human Genetics 62 473 - 480 2017.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Human Genetics
© 2017 The Japan Society of Human Genetics. Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by survival motor neuron gene mutations. Variant forms of SMA accompanied by additional clinical presentations have been classified as atypical SMA and are thought to be caused by variants in as yet unidentified causative genes. Here, we presented the clinical findings of two siblings with an SMA variant followed by progressive cerebral atrophy, and the results of whole-exome sequencing analyses of the family quartet that was performed to identify potential causative variants. We identified two candidate homozygous missense variants, R942Q in the tubulin-folding cofactor D (TBCD) gene and H250Q in the bromo-adjacent homology domain and coiled-coil containing 1 (BAHCC1) gene, located on chromosome 17q25.3 with an interval of 1.4 Mbp. The in silico analysis of both variants suggested that TBCD rather than BAHCC1 was likely the pathogenic gene (TBCD sensitivity, 0.68; specificity, 0.97; BAHCC1 sensitivity, 1.00; specificity, 0.00). Thus, our results show that TBCD is a likely novel candidate gene for atypical SMA with progressive cerebral atrophy. TBCD is predicted to have important functions on tubulin integrity in motor neurons as well as in the central nervous system.
DOI： 10.1038/jhg.2016.149
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Moritake H., Obara M., Saito Y., Kashimada A., Takagi M., Funakoshi-Tago M., Fukuyama T., Yoshioka M., Inoue A., Komatsu H., Nishitoh H., Kataoka H., Nunoi H.
Human Cell 30 88 - 97 2017.4
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Human Cell
© 2016, Japan Human Cell Society and Springer Japan. Major facilitator superfamily domain containing 2a (Mfsd2a) is a member of the major facilitator superfamily. Mfsd2a functions as a transporter for docosahexaenoic acid and also plays a role in the unfolded protein response (UPR) upon tunicamycin (TM) exposure. UPR is involved in the pathogenesis of various human diseases. TM and thapsigargin are representative experimental reagents that induce UPR. To elucidate the detailed function of Mfsd2a in UPR in vivo, we generated Mfsd2a-deficient mice and investigated the role of Mfsd2a during UPR induced by TM or thapsigargin. Phenotypically, Mfsd2a-deficient mice were small and short-lived. No gross anatomical abnormalities in Mfsd2a-deficient mice compared with the wild-type mice were exhibited. Embryonic fibroblasts derived from Mfsd2a-null mice failed to show induction of GRP78 and DDIT3 expressions upon TM exposure but not upon Tg exposure. This phenomenon could not be overcome despite the exposure under high TM concentration. Reconstitution of Mfsd2a in Mfsd2a-null MEF showed hypersensitivity to TM. Furthermore, we examined the physiological role of Mfsd2a against TM using an in vivo mouse model. DDIT3 induction by TM was drastically attenuated in both the liver and brain of Mfsd2a-deficient mice. These results reveal that Mfsd2a plays a critical role in UPR upon TM exposure.
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Kurogi Jun, Moritake Hiroshi, Yamada Ai, Kinoshita Mariko, Sawa Daisuke, Kamimura Sachiyo, Nakamura Yoshihiro, Chosa Etsuo, Nakata Hiroshi, Moriguchi Sayaka, Asada Yujiro, Nunoi Hiroyuki
The Japanese Journal of Pediatric Hematology / Oncology 54 ( 1 ) 54 - 57 2017
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Pediatric Hematology / Oncology
Osteosarcoma (OS) is the most common malignant bone tumor in children. Patients without metastasis are curable, whereas those with metastasis have a dismal prognosis. A recent clinical test has shown that bisphosphonate inhibits metastasis and improves the survival of osteosarcoma patients. We encountered the case of a 14-year-old male who suffered from OS of the left femur with multiple pulmonary nodules and treated with zoledronic acid (ZA) in addition to conventional chemotherapy. Histopathological examinations of the resected tumor revealed complete necrosis, suggesting a good response to preoperative chemotherapy. After the completion of chemotherapy, a few nodules disappeared, although most of the remaining pulmonary nodules showed no change in shape. Only hematological toxicity was observed during chemotherapy with ZA. The addition of ZA to conventional chemotherapy was safe in our patient. Evaluation of ZA efficacy was difficult, because the possibility that the pulmonary nodules were physiological intrapulmonary lymph nodes was high. Further experiences of treating Japanese patients will clarify the safety and efficacy of bisphosphonate for OS.
DOI： 10.11412/jspho.54.54
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Moritake H., Tanaka S., Nakayama H., Miyamura T., Iwamoto S., Shimada A., Terui K., Saito A., Shiba N., Hayashi Y., Tomizawa D., Taga T., Goto H., Hasegawa D., Horibe K., Mizutani S., Adachi S.
Pediatric Blood and Cancer 64 ( 10 ) 2017
Language：English Publishing type：Research paper (scientific journal)
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小児急性リンパ性白血病の very late relapse 例の予後 ―九州・山口小児がん治療研究グループ(KYCCSG)ALL 96/02 研究― Reviewed
野口磨依子,稲垣二郎,,岡本康裕,古賀友紀,大園秀一,新小田雄一,中山秀樹, 盛武 浩,堀田紀子,糸長伸能,野村優子,下之段秀美,市村卓也,日高靖文,河野嘉文
日本小児血液・がん学会雑誌 54 ( 5 ) 1046 - 1052 2017
Language：Japanese Publishing type：Research paper (scientific journal)
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Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation Reviewed
Konomoto T., Imamura H., Orita M., Tanaka E., Moritake H., Sato Y., Fujimoto S., Harita Y., Hisano S., Yoshiura K., Nunoi H.
Nephrology 21 ( 9 ) 765 - 773 2016.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Nephrology
© 2015 Asian Pacific Society of Nephrology Aim: Mutations of LMX1B cause nail-patella syndrome, a rare autosomal dominant disorder. Recently, LMX1B R246Q heterozygous mutations were recognised in nephropathy without extrarenal manifestation. The aim of this study was to clarify characteristics of nephropathy caused by R246Q mutation. Methods: Whole exome sequencing was performed on a large family with nonsyndromic autosomal dominant nephropathy without extrarenal manifestation. Clinical and histological findings of patients with LMX1B mutation were investigated. Results: LMX1B R246Q heterozygous mutation was identified in five patients over three generations. Proteinuria or haematoproteinuria was recognized by urinary screening from all patients in childhood. Proteinuria gradually increased to nephrotic levels and renal function decreased in adolescence. Two patients progressed to end-stage renal disease in adulthood. Renal histology demonstrated minimal change in childhood and focal segmental glomerulosclerosis in adulthood. Using electron microscopy, focal collagen deposition could be detected in glomeruli even when a “moth-eaten appearance” was not apparent in the glomerular basement membrane. In addition, podocin expression in glomerular podocytes was significantly decreased, even in the early stages of disease progression. Conclusion: Comprehensive genetic analyses and collagen or tannic acid staining may be useful for diagnosis of LMX1B-associated nephropathy. While renal prognosis of R246Q may be worse than that of typical NPS nephropathy, signs of podocytopathy can be detected during the infantile period; thus, childhood urinary screening may facilitate early detection.
DOI： 10.1111/nep.12666
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Noguchi M., Moritake H., Kamimura S., Sonoda M., Ishimura M., Inagaki J.
Bone Marrow Transplantation 53 ( 9 ) 1214 - 1217 2016.9
Language：English Publishing type：Research paper (scientific journal)
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Yamada A., Moritake H., Kinoshita M., Sawa D., Kamimura S., Iwamoto S., Yamashita Y., Inagaki J., Takahashi T., Shimada A., Obara M., Nunoi H.
Pediatrics International 58 ( 9 ) 905 - 908 2016.9
Language：English Publishing type：Research paper (scientific journal)
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Relapsed childhood acute myeloid leukemia patient with inversion of chromosome 16 harboring a low FLT3 internal tandem duplication allelic burden and KIT mutations Reviewed
Yamada A, Moritake H, Kinoshita M, Sawa, D, Kamimura S, Iwamoto S, Yamashita Y, Inagaki J, Takahashi T, Shimada A, Obara, M, Nunoi H
Pediatr Int 58 ( 9 ) 905 - 908 2016.9
Publishing type：Research paper (scientific journal)
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High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group Reviewed
Takahashi H.*, Watanabe T., Kinoshita A., Yuza Y., Moritake H., Terui K., Iwamoto S., Nakayama H., Shimada A., Kudo K., Taki T., Yabe M., Matsushita H., Yamashita Y., Koike K., Ogawa A., Kosaka Y., Tomizawa D., Taga T., Saito AM., Horibe K., Nakahata T., Miyachi H., Tawa A., Adachi S.
Br. J. Haematol. 2016.4
Language：English Publishing type：Research paper (scientific journal)
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Autoimmunity including intestinal Behçet's disease bearing the KRAS mutation in lymphocytes Reviewed
Moritake H, Takagi M, Kinoshita M, Ohara O, Yamamoto S, Moriguchi S, Nunoi H
Pediatrics 137 ( 3 ) e20152891 2016.3
Authorship：Lead author Publishing type：Research paper (scientific journal)
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Autoimmunity Including Intestinal Behcet Disease Bearing the KRAS Mutation in Lymphocytes: A Case Report. Reviewed
Moritake H, Takagi M, Kinoshita M, Ohara O, Yamamoto S, Moriguchi S, Nunoi H.
Pediatrics 2016.3
Language：English Publishing type：Research paper (scientific journal)
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Taga T., Watanabe T., Tomizawa D., Kudo K., Terui K., Moritake H., Kinoshita A., Iwamoto S., Nakayama H., Takahashi H., Shimada A., Taki T., Toki T., Ito E., Goto H., Koh K., Saito A., Horibe K., Nakahata T., Tawa A., Adachi S.
Pediatric Blood and Cancer 63 ( 2 ) 248 - 254 2016.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatric Blood and Cancer
© 2015 Wiley Periodicals, Inc. Background: On the basis of results of previous Japanese trials for myeloid leukemia in Down syndrome (ML-DS), the efficacy of risk-oriented therapy was evaluated in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-D05 study. Procedure: All patients received induction chemotherapy that consisted of pirarubicin, intermediate-dose cytarabine, and etoposide. Patients who achieved complete remission (CR) after initial induction therapy were stratified to the standard risk (SR) group and received four courses of reduced-dose intensification therapy. Patients who did not achieve CR were stratified to the high risk (HR) group and received intensified therapy that consisted of continuous or high-dose cytarabine. Results: A total of 72 patients were eligible and evaluated. One patient died of sepsis during initial induction therapy. Sixty-nine patients were stratified to SR and two patients to HR. No therapy-related deaths were observed during intensification therapy. The 3-year event-free and overall survival rates were 83.3% ± 4.4% and 87.5% ± 3.9 %, respectively. Age at diagnosis less than 2 years was a significant favorable prognostic factor for risk of relapse (P = 0.009). Conclusions: The attempt of risk-oriented prospective study for ML-DS was unsuccessful, but despite the dose reduction of chemotherapeutic agents, the overall outcome was good, and further dose reduction might be possible for specific subgroups.
DOI： 10.1002/pbc.25789
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Okamoto Y., Koga Y., Inagaki J., Ozono S., Ueda K., Shimoura M., Itonaga N., Shinkoda Y., Moritake H., Nomura Y., Nakayama H., Hotta N., Hidaka Y., Shimonodan H., Suga N., Tanabe T., Nakashima K., Fukano R., Kawano Y.
International Journal of Hematology 103 ( 2 ) 202 - 209 2016.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
© 2015, The Japanese Society of Hematology. In a previous study of childhood acute lymphoblastic leukemia (ALL) by the Kyushu–Yamaguchi Children’s Cancer Study Group, ALL-96, we achieved a 72.1 % 5-year event-free survival (EFS) and an 84.8 % 5-year overall survival (OS). In a subsequent study, ALL-02, we adopted a vincristine dexamethasone (VCR/DEX) pulse regimen as maintenance therapy in the context of the ALL-96 study using the same risk classification and treatment schedule. A total of 156 pediatric cases of ALL were treated with ALL-02. All of the patients were classified as standard-risk or high-risk. Risk stratification was based on white cell counts, immunophenotype, the presence of central nervous system (CNS) disease at diagnosis, organomegaly, and early treatment response (day 14 bone marrow status). The 7-year EFS and OS rates were 77.7 % (95 % CI 70.6–84.8 %) and 89.5 % (95 % CI 84.6–94.4 %), respectively. CNS 3 status [hazard ratio ( HR) = 5.0, p = 0.009] and high white blood cell count at diagnosis (HR = 2.6, p = 0.047) were risk factors for poor EFS in multivariate analysis. Our strategies to categorize patients into two risk groups, and to treat with a VCR/DEX pulse were feasible and reasonably effective treatments for pediatric ALL.
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Sporadic paraganglioma caused by de novo SDHB mutations in a 6-year-old girl Reviewed
Imamura H., Muroya K., Tanaka E., Konomoto T., Moritake H., Sato T., Kimura N., Takekoshi K., Nunoi H.
European Journal of Pediatrics 175 ( 1 ) 137 - 141 2016.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：European Journal of Pediatrics
© 2015, Springer-Verlag Berlin Heidelberg. Germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene (SDHB) cause susceptibility to paragangliomas and pheochromocytomas; however, it is exceedingly rare in childhood and especially in sporadic cases. We report the first Japanese pediatric case of paraganglioma with a de novo mutation in the SDHB gene. A 6-year-old girl with convulsions and hypertension was found to have a paravertebral abdominal tumor. Urinary and blood examinations revealed markedly elevated levels of norepinephrine. Following treatment for hypertension, the tumor was removed completely and histological findings were consistent with paraganglioma. Immunohistochemistry studies demonstrated the absence of SDHB protein expression, indicating an underlying SDH mutation with high probability. Germline mutation analysis of the SDHB gene revealed a heterozygous splice site mutation in intron 4 (C.423 + 1G > A). Subsequently, a second somatic genetic change was confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis, showing that deletion of the wild-type allele resulted in loss of function of SDHB. No germline mutations in SDHB were detected in her parents. Conclusion: Genetic testing should be considered for pediatric patients with paragangliomas, even in the absence of familial history, as closer lifelong screening to detect the development of malignancy will be required for patients with SDHB mutations.What is Known• Most sporadic cases of paraganglioma with SDHB mutations occur between adolescence and adulthood.• Screening methods for carriers of SDHB mutations assessing recurrence and detecting developing metastases are yet to be standardized.What is New• The current case of an extra-adrenal paraganglioma with a de novo SDHB mutation had an onset at 6 years.• We suggest much closer periodical observation for these high-risk children.
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Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS. Reviewed
Andoh T, Fujimoto T, Suzuki M, Sudo T, Sakurai Y, Tanaka H, Fujita I, Fukase N,?Moritake H, Sugimoto T, Sakuma T, Sasai H, Kawamoto T, Kirihata M, Fukumori Y, Akisue T, Ono K, Ichikawa H.
Appl Radiat Isot 2015.12
Language：English Publishing type：Research paper (scientific journal)
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Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia. Reviewed
Narita A, Muramatsu H, Sekiya Y, Okuno Y, Sakaguchi H, Nishio N, Yoshida N, Wang X, Xu Y, Kawashima N, Doisaki S, Hama A, Takahashi Y, Kudo K,?Moritake H, Kobayashi M, Kobayashi R, Ito E, Yabe H, Ohga S, Ohara A, Kojima S
Haematologica 2015.12
Language：English Publishing type：Research paper (scientific journal)
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Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST). Reviewed
Fujimoto T, Andoh T, Sudo T, Fujita I, Fukase N, Takeuchi T, Sonobe H, Inoue M, Hirose T, Sakuma T,?Moritake H, Sugimoto T, Kawamoto T, Fukumori Y, Yamamoto S, Atagi S, Sakurai Y, Kurosaka M, Ono K, Ichikawa H, Suzuki M.
Appl Radiat Isot 2015.12
Language：English Publishing type：Research paper (scientific journal)
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Long-Term Morbidity and Mortality in Children with Chronic Graft-versus-Host Disease Classified by National Institutes of Health Consensus Criteria after Allogeneic Hematopoietic Stem Cell Transplantation. Reviewed
Inagaki J,?Moritake H, Nishikawa T, Hyakuna N, Okada M, Suenobu S, Nagai K, Honda Y, Shimomura M, Fukano R, Noguchi M, Kurauchi K, Tanioka S, Okamura J.
Biol Blood Marrow Transplant 2015.11
Language：English Publishing type：Research paper (scientific journal)
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Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols Reviewed
Tomizawa D., Watanabe T., Hanada R., Horibe K., Horikoshi Y., Iwamoto S., Kinoshita A., Moritake H., Nakayama H., Shimada A., Taga T., Takahashi H., Tawa A., Terui K., Hori H., Kawano Y., Kikuta A., Manabe A., Adachi S.
International Journal of Hematology 102 ( 3 ) 318 - 326 2015.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
© 2015, The Japanese Society of Hematology. As past studies of adolescent and young adults (AYA) with acute myeloid leukemia (AML) reported conflicting results, we conducted a retrospective analysis using data from three Japanese pediatric AML studies. Among the 782 patients with de novo AML, 44 were classified as AYA (age ≥15 years at diagnosis), 164 as infants (0–1 year), 413 as younger children (2–11 years), and 161 as older children (12–14 years). While the 5-year event-free survival rate of AYA was not different among the groups, the five-year survival rate (54.7 %) was significantly lower than that of the other three groups (P = 0.019): 68.7 % for infants, 73.2 % for younger children, and 75.5 % for older children. No difference in the 5-year cumulative incidence of relapse was observed, but treatment-related death (TRD) of AYA was significantly higher (29.4 %) than that in infants (14.8 %), younger children (10.2 %), and older children (13.8 %). Multivariate analysis showed age ≥15 years old at diagnosis was associated with both poor survival rate and high TRD. Adolescents with AML had inferior survival due to a higher incidence of TRD, especially after failure of initial frontline treatment.
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Moritake H., Obara M., Sameshima N., Asada Y., Komatsu H., Hyakuna N., Sugita K., Ishida Y., Kato M., Tanizawa A., Deguchi T., Imamura T., Kitanaka A., Shimoda K., Kamimura S., Nunoi H.
International Journal of Hematology 102 ( 3 ) 349 - 356 2015.9
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
© 2015, The Japanese Society of Hematology. Bone marrow necrosis (BMN) is a rare phenomenon in children with malignancies, occurring most commonly in patients with acute lymphoblastic leukemia (ALL). The pathophysiology of this phenomenon has not been identified. We analyzed seven BMN cases with ALL in order to elucidate the underlying mechanism. Serum high-mobility group box 1 (HMGB1), cytochrome C, cytokines, and chemokines were measured, and real-time quantitative reverse transcription-polymerase chain reaction (RQ-RT-PCR) and immunochemistry of death-related molecules were analyzed using bone marrow samples. The serum levels of 17 of 27 cytokines and chemokines were found to be significantly elevated in patients with BMN in comparison to those in healthy volunteers; however, IFN-γ and IL-10 were not elevated. The cytokine pattern was different to that reported in hemophagocytic lymphohistiocytosis. The HMGB1 and cytochrome C levels in patients with BMN were not elevated. RQ-RT-PCR revealed significant overexpression of Fas-ligand, perforin, and granzyme B in the bone marrow of patients with ALL complicated with BMN compared with that in healthy volunteers and in patients with ALL without BMN. On immunohistochemistry, we identified leukemic cell-eliciting Fas-ligand and macrophage-eliciting TNF-α. Thus, no close relationship with massive necrosis or the intrinsic pathway of apoptosis was identified in the occurrence of BMN. These results suggest that the massive cell death phenomenon called BMN is partially induced by the extrinsic pathway of apoptosis.
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Psychosocial difficulties in adolescent and young adult survivors of childhood cancer Reviewed
Takei Y., Ogata A., Ozawa M., Moritake H., Hirai K., Manabe A., Suzuki S.
Pediatrics International 57 ( 2 ) 239 - 246 2015.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pediatrics International
© 2014 Japan Pediatric Society. Background With a large number of children surviving cancer worldwide, numerous investigations have assessed psychological and social adjustment among childhood cancer survivors. According to these studies, it is unclear whether childhood cancer survivors successfully adjust to daily life after being discharged from hospital, especially for adolescent and young adult survivors who have unique needs and concerns. The primary aim of this study was to identify the factors underlying psychosocial difficulties faced by adolescent and young adult survivors in their day-to-day lives after being discharged from hospital. Methods Semi-structured interviews were conducted. Twenty-five childhood cancer survivors were recruited from two regional cancer institutions in Japan. Content analysis was applied to the responses. Results Nineteen attributes were extracted and classified into four categories as follows: physical difficulties, interpersonal difficulties, behavioral difficulties, and uncertainty about the future. The attributes indicated by > 50% of the participants were "I am worried about not feeling well," "I have difficulty continuing treatment in daily life," "I have difficulty moving my body," "I have to be absent from school or work because of illness," and "I am left behind academically." Conclusions This study identified important factors of psychosocial day-to-day difficulties. Clinically, these results suggest that it is important to watch for these signs and to provide early support to survivors so that their daily life and development are not hindered by the treatment and its side-effects, and to offer long-term support focusing on individual patient characteristics such as sex, age, and cancer history.
DOI： 10.1111/ped.12495
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Proposed strategy for the use of high-dose chemotherapy with stem cell rescue and intrathecal topotecan without whole-brain irradiation for infantile classic medulloblastoma. Reviewed
Yamada A., Moritake H., Kamimura S., Yamashita S., Takeshima H., Nunoi H
Pediatr Blood & Cancer 2014.12
Language：English Publishing type：Research paper (scientific journal)
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プロプラノロールが著効した耳下腺部乳児血管腫の２例 Reviewed
下之段秀美、原田雅子、木下真理子、澤 大介、児嶋ひとみ、上村幸代、盛武 浩、松田圭三、布井博幸
宮崎県医師会雑誌 38 ( 2 ) 110 - 114 2014.9
Language：Japanese Publishing type：Case report
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Sakaguchi H., Nishio N., Hama A., Kawashima N., Wang X., Narita A., Doisaki S., Xu Y., Muramatsu H., Yoshida N., Takahashi Y., Kudo K., Moritake H., Nakamura K., Kobayashi R., Ito E., Yabe H., Ohga S., Ohara A., Kojima S.
Haematologica 99 ( 8 ) 1312 - 1316 2014.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Haematologica
Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5-16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41-69%) and 97% (95%CI: 87-99%), respectively. Median telomere length in responders was -0.4 standard deviation (SD) (-2.7 to +3.0 SD) and -1.5 SD (-4.0 to +1.6 (SD)) in non-responders (P < 0.001). Multivariate analysis showed that telomere length shorter than -1.0 SD (hazard ratio (HR): 22.0; 95%CI: 4.19-115; P < 0.001), platelet count at diagnosis less than 25×10 9 /L (HR: 13.9; 95%CI: 2.00-96.1; P=0.008), and interval from diagnosis to immunosuppressive therapy longer than 25 days (HR: 4.81; 95%CI: 1.15-20.1; P=0.031) were the significant variables for poor response to immunosuppressive therapy. Conversely to what has been found in adult patients, measurement of the telomere length of lymphocytes at diagnosis is a promising assay in predicting the response to immunosuppressive therapy in children with aplastic anemia. © 2014 Ferrata Storti Foundation.
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Nakayama H., Tabuchi K., Tawa A., Tsukimoto I., Tsuchida M., Morimoto A., Yabe H., Horibe K., Hanada R., Imaizumi M., Hayashi Y., Hamamoto K., Kobayashi R., Kudo K., Shimada A., Miyamura T., Moritake H., Tomizawa D., Taga T., Adachi S.
International Journal of Hematology 100 ( 2 ) 171 - 179 2014.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
The outcomes of children with relapsed acute myeloid leukemia (AML) are known to be poor, but remain obscure. We retrospectively analyzed 71 patients who had relapsed following first-line treatment under the AML99 protocol. We investigated the time and site of recurrence, response to re-induction therapy, and performance of hematopoietic stem cell transplantation (HSCT) in relapsed cases, and performed a multivariate analysis to identify prognostic factors. The 5-year overall-survival (OS) rate after relapse was 37 %. Of 71 patients, three died without any anti-leukemic therapy and two underwent allogeneic HSCT. The remaining 66 patients received re-induction chemotherapy, and 33 (50 %) achieved second CR (CR2). Twenty-two of 25 (88 %) late relapse patients and 11 of 41 (27 %) early relapse patients achieved CR2 (P < 0.001). Twenty-nine CR2 cases and 35 non-CR2 cases underwent allogeneic HSCT. The 5-year OS rate was significantly higher in patients who underwent HSCT in CR2 than those in non-CR2 (66 vs. 17 %, P < 0.000001). Multivariate analysis indicated that early relapse (P < 0.05) and the positivity of the FMS-like tyrosine kinase 3-internal tandem duplication (P < 0.05) were adverse prognostic factors for survival. In conclusion, the etiology of relapsed pediatric AML needs to be elucidated and effective chemotherapy should be administered to obtain CR2. © 2014 The Japanese Society of Hematology.
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Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: A Japanese retrospective study by the Kyushu-Yamaguchi Children’s Cancer Study Group. Reviewed
Moritake H, Kamimura S, Nunoi H, Nakayama H, Suminoe A, Inada H, Inagaki J, Yanai F, Okamoto Y, Shinkoda Y, Shimomura M, Itonaga N, Hotta N, Hidaka Y, Ohara O, Yanagimachi M, Nakajima N, Okamura J, Kawano Y
Int J Hematol 2014.7
Language：English Publishing type：Research paper (scientific journal)
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Andoh T., Fujimoto T., Sudo T., Suzuki M., Sakurai Y., Sakuma T., Moritake H., Sugimoto T., Takeuchi T., Sonobe H., Epstein A., Fukumori Y., Ono K., Ichikawa H.
Applied Radiation and Isotopes 88 59 - 63 2014.6
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Applied Radiation and Isotopes
Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS. © 2013 Elsevier Ltd.
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Kawano N., Tasaki A., Kuriyama T., Tahara Y., Yoshida S., Ono N., Himeji D., Yamashita K., Shibata Y., Goto T., Inoue T., Yokota-Ikeda N., Uezono S., Yuge A., Nishiguchi T., Kinjo T., Ogura Y., Beppu K., Ueda Y., Kinoshita M., Moritake H., Shimoda K., Ochiai H., Ueda A.
Internal Medicine 53 ( 3 ) 205 - 213 2014.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Internal Medicine
Objective Disseminated intravascular coagulation (DIC) is a clinical condition with high mortality that is characterized by the systemic activation of coagulation pathways resulting in multiple organ failure. Although no standard treatment for DIC has been established, recent reports have indicated that recombinant human soluble thrombomodulin (rTM) is effective against DIC. Methods To elucidate the clinical characteristics and outcomes of DIC, we retrospectively analyzed 92 DIC patients who were treated with rTM at Miyazaki Prefectural Hospital over a 4-year period (62 patients had infectious diseases and 30 patients had hematological diseases). A diagnosis of DIC was made based on the diagnostic criteria of the Japanese Association for Acute Medicine (JAAM) and Japanese Ministry of Health and Welfare (JMHW) for infectious diseases and hematological diseases, respectively. In addition to treating the underlying disease, rTM was administered for six consecutive days. Results In this study, 49 of the 92 DIC patients (53.3%) experienced resolution of DIC seven days after administration (46.8% patients with infectious disease and 66.7% with hematological disease). A higher survival rate was observed after a 28-day observation period in 69 of the 92 patients (75.0%) (72.6% of the patients with infectious disease and 80.0% of the patients with hematological disease). A lower DIC score at the initiation of rTM treatment was closely related to a higher rate of resolution of DIC. Conclusion Our findings indicate that rTM therapy is an effective, safe and feasible treatment for DIC patients. Furthermore, making an accurate and early diagnosis of DIC and providing subsequent immediate treatment with rTM may improve the resolution of DIC. © 2014 The Japanese Society of Internal Medicine.
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Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children's Cancer Study Group Reviewed
Hiroshi Moritake 1, Sachiyo Kamimura, Hiroyuki Nunoi, Hideki Nakayama, Aiko Suminoe, Hiroko Inada, Jiro Inagaki, Fumio Yanai, Yasuhiro Okamoto, Yuichi Shinkoda, Maiko Shimomura, Nobuyoshi Itonaga, Noriko Hotta, Yasufumi Hidaka, Osamu Ohara, Masakatsu Yanagimachi, Noriko Nakajima, Jun Okamura, Yoshifumi Kawano
Int J Hematol 2014.1
Authorship：Lead author Publishing type：Research paper (scientific journal)
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Excess treatment reduction including anthracyclins results in higher incidence of relapse in core binding factor acute myeloid leukemia in children. Reviewed
Tomizawa D., Tawa A., Watanabe T., Saito AM, Kudo K., Taga T, Iwamoto S., Shimads A., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Koh K., KIgasawa H., Kosaka Y., Miyachi H., Horibe K., Nakahata T., Adachi S
Leukemia 27 ( 12 ) 2413 - 2416 2013.12
Language：English Publishing type：Research paper (scientific journal)
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Appropriate dose reduction in induction therapy is essential for the treatment of infants with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group Reviewed
Tomizawa D., Tawa A., Watanabe T., Saito AM, Kudo K., Taga T, Iwamoto S., Shimads A., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Kiyokawa N., Isoyama K., MIzutani S., Hara J., Horibe K., Nakahata T., Adachi S
Int J Hematol 98 ( 5 ) 578 - 588 2013.11
Language：English Publishing type：Research paper (scientific journal)
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Ewing Sarcoma Cells Secrete EWS/Fli-1 Fusion mRNA via Microvesicles Reviewed
Tsugita M., Yamada N., Noguchi S., Yamada K., Moritake H., Shimizu K., Akao Y., Ohno T.
PLoS ONE 8 ( 10 ) 2013.10
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：PLoS ONE
Tumours defined as Ewing sarcoma (ES) constitute a group of highly malignant neoplasms that most often affect children and young adults in the first 2 decades of life. The EWS/Fli-1 fusion gene, a product of the translocation t(11;22) (q24; 12), is detected in 95% of ES patients. Recently, it was validated that cells emit a heterogeneous mixture of vesicular, organelle-like structures (microvesicles, MVs) into their surroundings including blood and body fluids, and that these MVs contain a selected set of tumor-related proteins and high levels of mRNAs and miRNAs. In this present study, we detected the Ewing sarcoma-specific EWS/Fli-1 mRNA in MVs from the culture medium of ES cell lines carrying t(11;22) (q24; 12). Also, we detected this fusion gene in approximately 40% of the blood samples from mice inoculated with xenografts of TC135 or A673 cells. These findings indicate the EWS/Fli-1 mRNA in MVs might be a new non-invasive diagnostic marker for specific cases of Ewing sarcoma. © 2013 Tsugita et al.
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YAMADA Ai, MORITAKE Hiroshi, SAWA Daisuke, SHIMONODAN Hidemi, KOJIMA Hitomi, KAMIMURA Sachiyo, NUNOI Hiroyuki
Rinsho Ketsueki 54 ( 4 ) 383 - 387 2013.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients.
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小児急性前骨髄球性白血病に対する三酸化ヒ素による治療 Reviewed
高橋浩之、盛武 浩、照井君典、井上彰子、落合秀匡、金井理恵、豊田秀実、松野良介、塩原正明、中尾朋平、富澤大輔、多賀崇、多和昭雄、足立壮一
日本小児血液・がん学会誌 50 ( 1 ) 32 - 37 2013.4
Language：Japanese Publishing type：Research paper (scientific journal)
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Yamada A., Moritake H., Sawa D., Shimonodan H., Kojima H., Kamimura S., Nunoi H.
[Rinshō ketsueki] The Japanese journal of clinical hematology 54 ( 4 ) 383 - 387 2013.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：[Rinshō ketsueki] The Japanese journal of clinical hematology
We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients.
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Boron neutron capture therapy (BNCT) selectively destroys human clear cell sarcoma in mouse model Reviewed
Fujimoto T., Andoh T., Sudo T., Fujita I., Moritake H., Sugimoto T., Sakuma Y., Akisue T., Kawabata S., Kirihara M., Suzuki M., Sakurai Y., Ono K., Fukumori Y., Kurosaka M., Ichikawa H.
Applied Radiation and Isotopes 73 96 - 100 2013.3
Language：English Publishing type：Research paper (scientific journal)
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EWS/ATF1 expression induces sarcomas from neural crest-derived cells in mice Reviewed
Yamada K., Ohno T., Aoki H., Semi K., Watanabe A., Moritake H., Shiozawa S., Kunisada T., Kobayashi Y., Toguchida J., Shimizu K., Hara A., Yamada Y.
Journal of Clinical Investigation 123 ( 2 ) 600 - 610 2013.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Clinical Investigation
Clear cell sarcoma (CCS) is an aggressive soft tissue malignant tumor characterized by a unique t(12;22) translocation that leads to the expression of a chimeric EWS/ATF1 fusion gene. However, little is known about the mechanisms underlying the involvement of EWS/ATF1 in CCS development. In addition, the cellular origins of CCS have not been determined. Here, we generated EWS/ATF1-inducible mice and examined the effects of EWS/ATF1 expression in adult somatic cells. We found that forced expression of EWS/ATF1 resulted in the development of EWS/ATF1-dependent sarcomas in mice. The histology of EWS/ATF1-induced sarcomas resembled that of CCS, and EWS/ATF1-induced tumor cells expressed CCS markers, including S100, SOX10, and MITF. Lineage-tracing experiments indicated that neural crest-derived cells were subject to EWS/ATF1-driven transformation. EWS/ATF1 directly induced Fos in an ERK-independent manner. Treatment of human and EWS/ATF1-induced CCS tumor cells with FOS-targeted siRNA attenuated proliferation. These findings demonstrated that FOS mediates the growth of EWS/ATF1-associated sarcomas and suggest that FOS is a potential therapeutic target in human CCS.
DOI： 10.1172/JCI63572
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Cytomegalovirus retinitis as an adverse immunological effect of pulses of vincristine and dexamethasone in maintenance therapy for childhood acute lymphoblastic leukemia Reviewed
Moritake H, Kamimura S, Kojima H, Shimonodan H, Harada M, Sugimoto T, Nao-I N, Nunoi H
Pediatr Blood Cancer 60 ( 2 ) 329 - 331 2013.2
Authorship：Lead author Publishing type：Research paper (scientific journal)
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Cytomegalovirus retinitis as an adverse immunological effect of pulses of vincristine and dexamethasone in maintenance therapy for childhood acute lymphoblastic leukemia. Reviewed
Moritake H.＊, Kamimura S., Kojima H., Shimonodan H., Harada M., Sugimoto T., Nao-I N., Nunoi H
Pediatric Blood and Cancer 60 ( 2 ) 329 - 331 2013.2
Language：English Publishing type：Research paper (scientific journal)
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Characteristics of Illness Perception and Psychosocial Adaptation of Survivors of Childhood Cancer Reviewed
TAKEI Yuko, OGATA Akiko, OZAWA Miwa, MORITAKE Hiroshi, HIRAI Kei, MANABE Atsushi, SUZUKI Shin-ichi
Japanese journal of behavior therapy 39 ( 1 ) 23 - 33 2013.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Association of Behavioral and Cognitive Therapies
The purpose of the present study was to examine the correlation between perceived illness experiences and psychosocial adaptation in adolescent childhood cancer survivors. The participants, 21 youth (7 boys, 14 girls; average age 15.8 years, SD 2.1) who were cancer patients attending pediatric outpatient clinics, were asked to participate in a semi-structured interview and complete the Pediatric Quality of Life (QOL) Inventory. The results indicated that psychosocial daily difficulties influenced their illness perception. Although the results were not statistically significant, positive perception might correlate positively with QOL, and negative perception or a despairing attitude might correlate negatively with QOL. Future research should investigate those influences in a quantitative study.
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Efficacy of Temozolomide in a Central Nervous System Relapse of Neuroblastoma with O6-Methylguanine Methyltransferase (MGMT) Promoter Methylation Reviewed
Yamada A., Moritake H.＊, Shimonodan H., Yokogami K., Takeshima H., Nunoi H
Journal of Pediatric Hematology and Oncology 35 ( 1 ) e38 - e41 2013.1
Language：English Publishing type：Research paper (scientific journal)
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Treatment outcome of non-Hodgkin lymphoma in childhood : KYCCSG NHL-89, 96 Reviewed
FUKANO Reiji, SUMINOE Aiko, MATSUZAKI Akinobu, INADA Hiroko, NAGATOSHI Yoshihisa, ISHII Eiichi, NAKAYAMA Hideki, KAWAKAMI Kiyoshi, MORITAKE Hiroshi, YANAI Fumio, ITONAGA Nobuyoshi, SUENOBU Soichi, KIKUCHI Masahiro, OKAMURA Jun, KAWANO Yoshifumi
Rinsho Ketsueki 53 ( 11 ) 1898 - 1905 2012.11
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hematology
Two consecutive treatment protocols, NHL-89 and NHL-96, for pediatric diffuse large cell lymphoma (DLC) and lymphoblastic lymphoma (LBL) were conducted between March 1989 and December 2004 by Kyushu-Yamaguchi Children's Cancer Study Group. Forty-two patients (DLC: 15, LBL: 27) and 34 patients (DLC: 8, LBL: 26) were enrolled in NHL-89 and NHL-96, respectively. DLC patients received induction therapy of high-dose methotrexate (MTX) followed by repeated administration of intermediate MTX. LBL patients received a 4-drug induction followed by intensification, consolidation with cranial radiotherapy (15 to 24Gy), and maintenance. The maintenance phase consisted of multiple drug treatment; including prednisolone, vincristine, cyclophosphamide, and 6-mercaptopurine. With a median follow-up of 150 months for NHL-89 and 90.5 months for NHL-96, the estimated event-free survival at 5 years are 76.2±6.6% and 67.7±8.0%, respectively. Both studies improved the prognosis of DLC and LBL over our previous study of NHL-858.
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[Treatment outcome of non-Hodgkin lymphoma in childhood: KYCCSG NHL-89, 96]. Reviewed
Fukano R., Suminoe A., Matsuzaki A., Inada H., Nagatoshi Y., Ishii E., Nakayama H., Kawakami K., Moritake H., Yanai F., Itonaga N., Suenobu S., Kikuchi M., Okamura J., Kawano Y.
[Rinshō ketsueki] The Japanese journal of clinical hematology 53 ( 11 ) 1898 - 1905 2012.11
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：[Rinshō ketsueki] The Japanese journal of clinical hematology
Two consecutive treatment protocols, NHL-89 and NHL-96, for pediatric diffuse large cell lymphoma (DLC) and lymphoblastic lymphoma (LBL) were conducted between March 1989 and December 2004 by Kyushu-Yamaguchi Children's Cancer Study Group. Forty-two patients (DLC: 15, LBL: 27) and 34 patients (DLC: 8, LBL: 26) were enrolled in NHL-89 and NHL-96, respectively. DLC patients received induction therapy of high-dose methotrexate (MTX) followed by repeated administration of intermediate MTX. LBL patients received a 4-drug induction followed by intensification, consolidation with cranial radiotherapy (15 to 24Gy), and maintenance. The maintenance phase consisted of multiple drug treatment; including prednisolone, vincristine, cyclophosphamide, and 6-mercaptopurine. With a median follow-up of 150 months for NHL-89 and 90.5 months for NHL-96, the estimated event-free survival at 5 years are 76.2±6.6% and 67.7±8.0%, respectively. Both studies improved the prognosis of DLC and LBL over our previous study of NHL-858.
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Acute myeloid leukemia in clinical practice: a retrospective population-based cohort study in Miyazaki Prefecture, Japan Reviewed
Matsunaga T, Yamashita K, Kubuki Y, Toyama T, Imataki O, Maeda K, Kawano N, Satou S, Kawano H, Ishizaki J, Yoshida S, Kameda T, Sasaki T, Sekine M, Kamiunten A, Taniguchi Y, Hidaka T, Katayose K, K-Shimoda H, Shide K, Yamamoto S, Moritake H, Nunoi H, Maki
International Journal of Hematology 96 ( 3 ) 342 - 349 2012.9
Language：English Publishing type：Research paper (scientific journal)
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Taga T., Saito A., Kudo K., Tomizawa D., Terui K., Moritake H., Kinoshita A., Iwamoto S., Nakayama H., Takahashi H., Tawa A., Shimada A., Taki T., Kigasawa H., Koh K., Adachi S.
Blood 120 ( 9 ) 1810 - 1815 2012.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Blood
Myeloid leukemia in Down syndrome (ML-DS) is associated with good response to chemotherapy and favorable prognosis. Because little research has been focused on refractory/relapsed (R/R) cases, we conducted a retrospective analysis for R/R ML-DS. Among ML-DS patients diagnosed between 2000 and 2010 in Japan, 26 relapsed (25 in the BM and 1 in the skin), and 3 refractory patients were enrolled. The male/female ratio was 18/11. The median age at initial diagnosis of ML-DS was 2 years, and the median time to relapse was 8.6 months. Each patient initially had been treated with ML-DS-specific protocols. Thirteen of the 26 patients achieved complete remission with various kinds of reinduction chemotherapies; 2 of 8 survived without further recurrence after receiving allogeneic hematopoietic stem cell transplantation, and 4 of 5 maintained complete remissions with chemotherapy alone. Treatment failures mostly were associated with disease progression rather than treatment-related toxicities. The 3-year OS rate was 25.9% ± 8.5%. A longer duration from initial diagnosis to relapse was a significant favorable prognostic factor (P < .0001). We conclude that clinical outcome for patients with R/R ML-DS generally are unfavorable, even in those receiving hematopoietic stem cell transplantation. Novel methods to identify poor prognostic factors for ML-DS are necessary. © 2012 by The American Society of Hematology.
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The Perceived Cancer Experience in Japanese Childhood Cancer Patients : A Qualitative Study Reviewed
TAKEI Yuko, OGATA Akiko, HIRAI Kei, OZAWA Miwa, MORITAKE Hiroshi, MANABE Atushi, SUZUKI Shin-ichi
52 ( 7 ) 638 - 645 2012.7
Language：Japanese Publishing type：Research paper (scientific journal)
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Acute megakaryoblastic leukemia and severe pulmonary fibrosis in child with Down syndrome: Successful treatment with ultra low-dose cytarabine using GATA1 mutation to monitor minimal residual disease Reviewed
Moritake H, Yamada A, Kimoto Y, Sawa D, Shimonodan H, Nunoi H
Am J Hematol 87 ( 4 ) 447 - 450 2012.4
Authorship：Lead author Publishing type：Research paper (scientific journal)
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Acute megakaryoblastic leukemia and severe pulmonary fibrosis in child with Down syndrome: Successful treatment with ultra low-dose cytarabine using GATA1 mutation to monitor minimal residual disease. Reviewed
Moritake H.＊, Yamada A., Kimoto Y., Sawa D., Shimonodan H., Nunoi H
American Journal of Hematology 87 ( 4 ) 457 - 450 2012.4
Language：English Publishing type：Research paper (scientific journal)
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Concomitant transient erythroblastopenia of childhood with neonatal hepatitis. Reviewed
Moritake H, Hidaka F, Kamimura S, Kojima H, Shimonodan H, Nunoi H.
Pediatrics International 54 ( 1 ) 147 - 150 2012.2
Language：English Publishing type：Research paper (scientific journal)
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Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies. Reviewed
Fujimoto T, Andoh T, Sudo T, Fujita I, Imabori M, Moritake H, Sugimoto T, Sakuma Y, Takeuchi T, Sonobe H, Epstein AL, Akisue T, Kirihata M, Kurosaka M, Fukumori Y, Ichikawa H.
Applied Radiation Isotopes 69 ( 12 ) 1713 - 1716 2011.12
Language：English Publishing type：Research paper (scientific journal)
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Andoh T., Fujimoto T., Sudo T., Fujita I., Imabori M., Moritake H., Sugimoto T., Sakuma Y., Takeuchi T., Kawabata S., Kirihata M., Akisue T., Yayama K., Kurosaka M., Miyatake S., Fukumori Y., Ichikawa H.
Applied Radiation and Isotopes 69 ( 12 ) 1721 - 1724 2011.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Applied Radiation and Isotopes
Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of 10 B (45-74ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of l-BPA-fructose complex (500mg BPA/kg). © 2011 Elsevier Ltd.
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C-MYC rearrangement may induce an aggressive phenotype in anaplastic lymphoma kinase positive anaplastic large cell lymphoma: Identification of a novel fusion gene ALO17/C-MYC Reviewed
Moritake H, Shimonodan H, Marutsuka K, Kamimura S, Kojima H, Nunoi H
Am J Hematol. 86 ( 1 ) 75 - 78 2011.1
Authorship：Lead author Publishing type：Research paper (scientific journal)
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Moritake H., Shimonodan H., Marutsuka K., Kamimura S., Kojima H., Nunoi H.
American Journal of Hematology 86 ( 1 ) 75 - 78 2011.1
Language：English Publishing type：Research paper (scientific journal)
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P1-12 小児がん患者における病気のとらえ方と退院後の困難の関連性の検討(一般演題(ポスター発表),切れる最新の理論と途切れない地道な実践) Reviewed
武井 優子, 尾形 明子, 小澤 美和, 盛武 浩, 真部 淳, 平井 啓, 鈴木 伸一
日本行動療法学会大会発表論文集 ( 36 ) 164 - 165 2010.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：一般社団法人日本認知・行動療法学会
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Randomized trial to compare LSA2L2 type maintenance therapy to daily 6-mercaptopurine and weekly methotrexate with vincristine and dexamethasone pulse for children with acute lymphoblastic leukemia. 共著 Reviewed
Nagatoshi Y, Moritake H, 他
Pediatr. Blood Cancer 55 ( 2 ) 239 - 247 2010.8
Language：English Publishing type：Research paper (scientific journal)
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Cytomagalovirus infection mimicking juvenile myelomonocytic leukemia showing hypersensitivity to granulocyte-macrophage colony stimulating factor.（共著） Reviewed
Moritake H. 他
Pediatric Blood & Cancer 53 ( 7 ) 1324 - 1326 2009.12
Language：English Publishing type：Research paper (scientific journal)
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Cytomegalovirus infection mimicking juvenile myelomonocytic leukemia showing hypersensitivity to granulocyte-macrophage colony stimulating factor Reviewed
Moritake H, Ikeda T, Manabe A, Kamimura S, Nunoi H
Pediatr Blood Cancer 53 ( 7 ) 1324 - 1326 2009.12
Authorship：Lead author Publishing type：Research paper (scientific journal)
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PP-196 Xp11.2転座/TFE3融合遺伝子関連腎癌の1例(腎腫瘍/症例2,一般演題ポスター,第97回日本泌尿器科学会総会) Reviewed
向井 尚一郎, 上村 敏雄, 田中 弘之, 盛武 浩, 長野 正史, 蓮井 良浩
日本泌尿器科学会雑誌 100 ( 2 ) 2009
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：一般社団法人 日本泌尿器科学会
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Jak2 FERM domain interaction with the erythropoietin receptor regulates Jak2 kinase activity Reviewed
Funakoshi-Tago M, Pelletier S, Moritake H, Parganas E, Ihle JN.
Mol Cell Biol 28 ( 5 ) 1792 - 1801 2008.3
Language：English Publishing type：Research paper (scientific journal)
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眼窩腫瘍を初発症状とした小児の急性巨核芽球性白血病の１例 Reviewed
白坂陽子,中馬秀樹,直井信久,満木ひとみ,盛武 浩
眼科 48 511 - 516 2006
Language：Japanese Publishing type：Case report
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Prognostic factors for relapsed childhood acute lymphoblastic leukemia: impact of allogeneic stem cell transplantation--a report from the Kyushu-Yamaguchi Children's Cancer Study Group Reviewed
Matsuzaki A, Nagatoshi Y, Inada H, Nakayama H, Yanai F, Ayukawa H, Kawakami K, Moritake H, Suminoe A, Okamura J
Pediatr Blood Cancer 45 ( 2 ) 111 - 120 2005.8
Language：English Publishing type：Research paper (scientific journal)
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Kuroda H., Moritake H., Sawada K., Kuwahara Y., Imoto I., Inazawa J., Sugimoto T.
Cancer Genetics and Cytogenetics 158 ( 2 ) 172 - 179 2005.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer Genetics and Cytogenetics
Malignant rhabdoid tumors (MRT) of the liver are rare. A few liver MRT cell lines have been established but none has been characterized in detail. Here we describe a new MRT cell line from the liver, which is designated MP-MRT-AN, and describe it in detail. Immunohistochemical assays detected the expression of vimentin and cytokeratin but they were negative for neurofilament, desmin, α-smooth muscle actin, α-sarcomeric actin, and smooth muscle myosin heavy chains SM1 and SM2. RT-PCR assays revealed that this cell line did not express smooth muscle myosin heavy chain isoforms or MyoD1. No aberration was identified in 22q by G-banded analysis; however, the hSNF5/INI1 gene, a suppressor gene of MRT that maps to 22q11.2, was homozygously deleted from exons 1 to 5 in this cell line. Furthermore, the expression of another tumor suppressor gene, p16 (CDKN2A), was not detected by RT-PCR. This raises the possibility that the aggressive phe notype of malignant rhabdoid tumors is caused by the loss of two or more tumor suppressor genes. © 2005 Elsevier Inc. All rights reserved.
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Kosaka Y., Koh K., Kinukawa N., Wakazono Y., Isoyama K., Oda T., Hayashi Y., Ohta S., Moritake H., Oda M., Nagatoshi Y., Kigasawa H., Ishida Y., Ohara A., Hanada R., Sako M., Sato T., Mizutani S., Horibe K., Ishii E.
Blood 104 ( 12 ) 3527 - 3534 2004.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Blood
Forty-four infants with acute lymphoblastic leukemia (ALL) characterized by MLL gene rearrangements were treated on a protocol of intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT) between November 1998 and June 2002. The remission induction rate was 91.0%, and the 3-year overall survival and event-free survival (EFS) rates, with 95% confidence intervals, were 58.2% (43.5%-72.9%) and 43.6% (28.5%-58.7%), respectively. Univariate analysis of EFS by presenting features indicated a poorer outcome in patients younger than 6 months of age with high white blood cell counts (≥ 100 × 10 9 /L; EFS rate, 9.4% versus 55.1% for all others, P = .0036) and in those with central nervous system invasion (EFS rate, 10.0% versus 56.9% for all others, P = .0073). The 3-year posttransplantation EFS rate for the 29 patients who underwent HSCT in first remission was 64.4% (46.4%-82.4%). In this subgroup, only the timing of HSCT (first remission versus others) was a significant risk factor by multivariate analysis (P < .0001). These results suggest that early introduction of HSCT, possibly with a less toxic conditioning regimen, may improve the prognosis for infants with MLL + ALL. Identification of subgroups or patients who respond well to intensified chemotherapy alone should have a high priority in future investigations. © 2004 by The American Society of Hematology.
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Residential proximity to high-voltage power lines and risk of childhood hematological malignancies Reviewed
Mizoue T., Onoe Y., Moritake H., Okamura J., Sokejima S., Nitta H.
Journal of Epidemiology 14 ( 4 ) 118 - 123 2004.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Epidemiology
Background: Epidemiologic studies of electromagnetic fields and childhood cancers have focused on home exposure. The authors investigated whether residence in districts near high-voltage power lines is associated with childhood hematological malignancies, using small area analysis. Methods: Among 50,000 children in a city in Japan, 14 cases aged younger than 15 years were diagnosed with these malignancies in the period from 1992 through 2001. A total of 294 districts constituting this city were classified according to their proximity to high-voltage power lines (either 66 kV or 220 kV). Mantel-Haenszel rate ratio is used to calculate incidence rate ratio and its 95% confidence interval (CI). Results: Compared to districts of which no area fell within 300 m of high-voltage power lines, districts in which at least 50% of the area fell within 300 m of high-voltage power lines demonstrated an increased risk (incidence rate ratio: 2.2; 95% CI: 0.5-9.0). The association was strengthened for homes in which patients had resided for the longest interval of their lives (incidence rate ratio: 3.4; 95% CI: 0.9-13.2). Point-in-time measurements showed no increase in magnetic field levels for patient homes in districts near the lines. Conclusion: An increased, albeit nonsignificant, risk of childhood hematological malignancies associated with residential proximity to high-voltage power lines warrants further investigations. Copyright © 2005 by Japan Epidemiological Association.
DOI： 10.2188/jea.14.118
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Viral infections in juvenile myelomonocytic leukemia: prevalence and clinical implications. Reviewed
Manabe A,Yoshimasu T,Ebihara Y,Yagasaki H,Wada M,Ishikawa K,Hara J,Koike K,盛武 浩,Park YD,Tsuji K,Nakahata T
J Pediatr Hematol Oncol 26 636 - 641 2004.10
Language：English Publishing type：Research paper (scientific journal)
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MORITAKE Hiroshi, MITSUKI Hitomi, HIDAKA Fumio, TOYAMA Seiya, KAMIMURA Sachiyo, KONOMOTO Takao, SONODA Tohru, KANEKO Yasuhiko, NUNOI Hiroyuki
41 ( 1 ) 130 - 133 2004
Authorship：Lead author Language：Japanese Publishing type：Case report
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Moritake H., Sugimoto T., Kuroda H., Hidaka F., Takahashi Y., Tsuneyoshi M., Yoshida M., Cui Q., Akiyoshi K., Izumi T., Nunoi H.
Cancer Genetics and Cytogenetics 146 ( 2 ) 102 - 109 2003.10
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer Genetics and Cytogenetics
Askin tumor is a malignant small round cell tumor that originates from the thoracopulmonary region and is a member of Ewing sarcoma family of tumors (ESFT). Only a few Askin tumor cell lines have been established. An Askin tumor cell line, designated MP-ASKIN-SA, was established from the left thoracic tumor of a 13-year-old Japanese boy. ESFT is known to have a high rate of distant metastases at diagnosis. The genes controlling the spread of ESFT cells, however, have not been elucidated. G-banding chromosome analysis revealed that the MP-ASKIN-SA cell line has complex chromosomal abnormalities including trisomy 8. The EWS/FLI1 chimeric transcript and c-myc overexpression were revealed by the reverse transcriptase-polymerase chain reaction and Northern blot analysis. Furthermore, we investigated the expression of the focal adhesion kinase (FAK) gene in the ESFT cell lines using Northern blot analysis. In addition to the MP-ASKIN-SA cell line, six Ewing sarcoma cell lines, one peripheral nerve sheath tumor cell line, and two Askin tumor cell lines were analyzed. All ESFT cell lines, including MP-ASKIN-SA, expressed five- to twenty-eight-fold-increased values of FAK, as compared with fibroblasts obtained from the bone marrow of a healthy volunteer. These results raise the possibility that the overexpression of c-myc and FAK are involved in the poor prognosis of ESFT. © 2003 Elsevier Inc. All rights reserved.
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Moritake H., Kamimura S., Akiyoshi K., Nagatoshi Y., Chuman H., Okamura J.
Medical and Pediatric Oncology 40 ( 3 ) 187 - 188 2003.3
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Medical and Pediatric Oncology
DOI： 10.1002/mpo.10115
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.Newly established clear cell sarcoma (malignant melanoma of soft parts) cell line expressing melanoma-associated Melan-A antigen and overexpressing C-MYC oncogene Reviewed
Moritake H, Sugimoto T, Asada Y, Yoshida MA, Maehara Y, Epstein AL, Kuroda H.Newly established clear cell sarcoma (malignant melanoma of soft parts) cell line expressing melanoma-associated Melan-A antigen and overexpressing C-MYC oncogene.Cancer Genet Cytogenet. 2002 May;135(1):48-56.[査読有]
Cancer Genetics and Cytogenetics 135 ( 1 ) 48 - 56 2002.6
Publishing type：Research paper (scientific journal)
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Analysis of PTEN/MMAC1 alteration in neuroblastoma Reviewed
H Moritake, Y Horii, H Kuroda, T Sugimoto
Cancer Genet Cytogenet 125 ( 2 ) 151 - 155 2001.3
Authorship：Lead author Publishing type：Research paper (scientific journal)
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Analysis of PTEN/MMAC1 alteration in neuroblastoma Reviewed
Moritake H, Horii Y, Kuroda H, Sugimoto T
Cancer Genet Cytogenet 2001.3
Language：English Publishing type：Research paper (scientific journal)
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Signal Transduction Pathways through TRK-A and TRK-B Receptors in Human Neuroblastoma Cells Reviewed
SUGIMOTO Tohru, KURODA Hiroshi, HORII Yoshihiro, MORITAKE Hiroshi, TANAKA Takeo, HATTORI Seisuke
Japanese journal of cancer research : gann 92 ( 2 ) 152 - 160 2001.2
Language：Japanese Publishing type：Research paper (scientific journal)
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A case report of aneurysmal bone cyst of the thoracic spine caused paraplegia Reviewed
HIDAKA Fumio, MORITAKE Hiroshi, KURODA Hiroshi, HORII Yoshihiro, SUGIMOTO Tohru, FUJIME Kenichi, GOYA Tomokazu, WAKISAKA Shinichirou, NABESHIMA Kazuki, KOONO Masashi
37 ( 4 ) 516 - 519 2000.12
Language：Japanese Publishing type：Case report
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Renin producing hepatoblastoma Reviewed
Moritake H, Taketomi A, Kamimura S, Ikuno Y, Seo Y, Fukuda T, Iguchi H, Okamura J.
J Pediatr Hematol Oncol 2000.2
Language：English Publishing type：Research paper (scientific journal)
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Renin producing hepatoblastoma Reviewed
Moritake H, Taketomi A, Kamimura S, Ikuno Y, Seo Y, Fukuda T, Iguchi H, Okamura J
J Pediatr Hematol Oncol 22 ( 1 ) 78 - 80 2000.1
Authorship：Lead author Publishing type：Research paper (scientific journal)
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Moritake H., Ikuno Y., Tasaka H., Koga H., Miyazaki S., Okamura J.
Bone Marrow Transplantation 21 ( 7 ) 725 - 726 1998.4
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Bone Marrow Transplantation
A 10-year-old boy with metastatic rhabdomyosarcoma had an HLA-identical sibling and received an allogeneic BMT. Recurrence was detected in the BM as the only site of treatment failure 12 months after BMT. Donor leukocyte infusion (DLI) was chosen as salvage therapy. Although sufficient cells (a total of 29.7 x 10 7 /kg) were infused, no signs of acute GVHD nor BM aplasia occurred and the patient died of disease progression 9 months after DLI.
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化学療法と放射線療法が奏効した鼻咽頭癌の16歳男児例 Reviewed
堀井由博,黒田啓史,児玉由紀子,紺谷幸代,河野慶一郎,盛武 浩,松田圭二,浅田祐士郎,小野誠治,杉本 徹
小児がん 35 248 - 518 1998
Language：Japanese Publishing type：Case report
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左アキレス腱に原発したClear cell sarcomaの13歳女児例 Reviewed
河野慶一郎,澤田一美,盛武 浩,黒田啓史,堀井由博,桑原 茂,浅田祐士郎,住吉昭信,杉本 徹
小児がん 35 532 - 535 1998
Language：Japanese Publishing type：Case report
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Ewing肉腫ファミリー腫瘍におけるキメラ産物の検出 Reviewed
堀井由博,杉本 徹,黒田啓史,盛武 浩,紺谷幸代,江口春彦,田代 聡,宮崎澄雄
小児がん 34 191 - 195 1997
Language：English Publishing type：Research paper (scientific journal)
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腸重積を合併した悪性リンパ腫の6歳男児例 Reviewed
盛武 浩,井上 忍,此元隆雄,山崎俊輔,杉本 徹,丸山賢幸,崎浜國治,東秀史,瀬戸口敏明,丸塚浩助,住吉昭信:
宮崎県医師会医学雑誌 20 89 - 93 1996
Language：Japanese Publishing type：Case report
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Henoch-Schonlein紫斑病の臨床像を呈した溶連菌感染後急性糸球体腎炎の1例 Reviewed
清 保博,黒川聡子,盛武 浩,大野拓郎,西口俊裕,三宅和昭,浜田恵亮
日本小児科学会雑誌 99 1476 - 1480 1995
Language：Japanese Publishing type：Case report
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ヒトヘルペスウイルス6型の初感染による脳炎・脳症の臨床像 Reviewed
福永一美,糸数直哉,盛武 浩,井上 忍,大庭健一,園田 徹,杉本 徹
小児科臨床 20 89 - 93 1995
Language：Japanese Publishing type：Research paper (scientific journal)
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心因性の歩行障害を示した片側性モヤモヤ病の1例 Reviewed
盛武 浩,福永一美,糸数直哉,井上 忍,杉本 徹
小児科臨床 48 2223 - 2226 1995
Language：English Publishing type：Case report
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乳児マススクリーニングにて発見され治療終了2年5ヵ月後に再発した神経芽腫の1例 Reviewed
盛武 浩,日高文郎,児玉由紀子,紺谷幸代,大隅暁美,黒田啓史,堀井由博,杉本 徹,恒吉正澄,田中丈夫
小児がん 35 240 - 243 1988
Language：Japanese Publishing type：Research paper (scientific journal)