論文 - 下田 和哉
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Fauzi Y.R., Nakahata S., Shimoda K., Matsuura T., Hagiwara S., Inoue K., Moritake H., Morishita K.
Biochemical and Biophysical Research Communications 756 151564 2025年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：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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Effects of tucidinostat in adult T-cell leukemia/lymphoma in clinical practice 査読あり
Kamiunten A., Kameda T., Sekine M., Kawano H., Toyama T., Akizuki K., Kawano N., Maeda K., Sato S., Takeuchi M., Ishizaki J., Nagamine K., Kuroki A., Ikeda R., Matsumoto K., Karasawa M., Tahira Y., Uchida T., Shimoda H., Hidaka T., Yamashita K., Yamaguchi H., Kubuki Y., Shimoda K., Shide K.
International Journal of Hematology 2025年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy with a poor prognosis. We conducted a retrospective study across six institutions in Miyazaki Prefecture, Japan, to assess the efficacy of tucidinostat in patients with relapsed/refractory ATL who had not undergone transplantation. Between October 2021 and July 2023, 24 patients aged 41 to 88 years (median, 73.4 years) who had undergone prior therapies, including intensive chemotherapy (79.2%) and mogamulizumab immunotherapy (79.2%), received tucidinostat. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated as key outcomes. ORR and DCR reached 54.2% and 91.7%, respectively. The median PFS was 3.95 months, and OS was 8.04 months, which were not inferior to the results of a phase IIb study. The influential factors for PFS were age ≥ 75 years and high soluble IL-2 receptor (sIL-2R) levels above 5000 U/mL at the start of treatment. Favorable patients without these factors achieved a PFS of 11.4 months. Treatment-related adverse events were mainly hematologic but were managed over the course of treatment. Our findings indicate that tucidinostat provides survival benefits in patients with relapsed/refractory ATL in clinical practice and highlight key clinical factors for better outcomes.
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Takahashi N., Takenaka K., Iriyama N., Kirito K., Kawaguchi T., Kimura S., Shimoda K.
International Journal of Hematology 121 ( 1 ) 5 - 38 2025年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
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Yoshikawa N., Ehara Y., Yamada Y., Matsusaki Y., Shimoda K., Ikeda R.
Scientific Reports 15 ( 1 ) 3364 2025年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Intra-patient variability in immunosuppressive blood drug concentrations is a potential biomarker in managing organ transplant patients. However, the association between the time in therapeutic range of tacrolimus blood concentrations and its efficacy in preventing graft-versus-host disease remains unknown. In this study, we analyzed the relationship between the time in therapeutic range of tacrolimus blood concentrations and its efficacy in acute graft-versus-host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation. Eligible patients administered tacrolimus were categorized into two groups based on the grade of acute graft-versus-host disease, and propensity score matching was performed using graft-versus-host disease prophylaxis protocols and days to the disease onset to compare time in therapeutic range. In patients with tacrolimus blood concentration therapeutic range ≥ 10 ng/mL, time in therapeutic range during the first 4 weeks post-transplantation was significantly lower in the Grade II–III than in the Grade 0–I group. Among propensity score matching-extracted patients, the Grade II–III group had significantly lower time in therapeutic range during the first 2 and 4 weeks post-transplantation. Our results suggest that high time in therapeutic range early post-transplantation, particularly within 4 weeks, may avert the severity of acute graft-versus-host disease.
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C-Mannosyl tryptophan is a novel biomarker for thrombocytosis of myeloproliferative neoplasms 査読あり
Tabata S., Yamashita Y., Inai Y., Morita S., Kosako H., Takagi T., Shide K., Manabe S., Matsuoka T.A., Shimoda K., Sonoki T., Ihara Y., Tamura S.
Scientific Reports 14 ( 1 ) 18858 2024年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
C-Mannosyl tryptophan (CMW), a unique glycosylated amino acid, is considered to be produced by degradation of C-mannosylated proteins in living organism. Although protein C-mannosylation is involved in the folding and secretion of substrate proteins, the pathophysiological function in the hematological system is still unclear. This study aimed to assess CMW in the human hematological disorders. The serum CMW levels of 94 healthy Japanese workers were quantified using hydrophilic interaction liquid chromatography. Platelet count was positively correlated with serum CMW levels. The clinical significance of CMW in thrombocytosis of myeloproliferative neoplasms (T-MPN) including essential thrombocythemia (ET) were investigated. The serum CMW levels of the 34 patients with T-MPN who presented with thrombocytosis were significantly higher than those of the 52 patients with control who had other hematological disorders. In patients with T-MPN, serum CMW levels were inversely correlated with anemia, which was related to myelofibrosis (MF). Bone marrow biopsy samples were obtained from 18 patients with ET, and serum CMW levels were simultaneously measured. Twelve patients with bone marrow fibrosis had significantly higher CMW levels than 6 patients without bone marrow fibrosis. Collectively, these results suggested that CMW could be a novel biomarker to predict MF progression in T-MPN.
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Long-term safety and efficacy of ropeginterferon alfa-2b in Japanese patients with polycythemia vera 査読あり
Kirito K., Sugimoto Y., Gotoh A., Takenaka K., Ichii M., Inano T., Shirane S., Ito M., Zagrijtschuk O., Qin A., Kawase H., Sato T., Komatsu N., Shimoda K.
International Journal of Hematology 120 ( 6 ) 675 - 683 2024年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
Ropeginterferon alfa-2b (ropegIFN), a new-generation interferon-based agent, has been approved in Japan for patients with polycythemia vera (PV) who are ineligible for or respond inadequately to conventional treatment. However, long-term outcomes with ropegIFN in Japanese patients have not been reported. This extension of a phase 2 study of ropegIFN in Japanese patients with PV aimed to determine its long-term safety/efficacy, and changes over time in JAK2 V617F allele burden. Here, we report data from the phase 2 study and subsequent extension over a period of 36 months. The primary endpoint was the complete hematologic response (CHR) maintenance rate without phlebotomy (hematocrit value < 45% without phlebotomy during the previous 12 weeks, platelet count ≤ 400 × 109/L, and white blood cell count ≤ 10 × 109/L). The CHR maintenance rates were 8/27 (29.6%), 18/27 (66.7%), and 22/27 (81.5%) at 12, 24, and 36 months, respectively. No thrombotic or hemorrhagic events occurred. The median allele burden change from baseline was − 74.8% at 36 months. All patients experienced adverse events; 25/27 (92.6%) experienced adverse drug reactions (ADRs), but no serious ADRs or deaths occurred. This interim analysis demonstrated the safety and efficacy of ropegIFN over 36 months in Japanese patients with PV.
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Kitamura A., Yanagi S., Shide K., Sato Y., Kamiunten A., Yamanari Y., Kitamura A., Sumiyoshi M., Oda Y., Tsubouchi H., Shimoda K., Miyazaki T.
American Journal of Case Reports 25 e945804 2024年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Case Reports
Patient: Male, 32-year-old Final Diagnosis: B-acute lymphoblastic leukemia Symptoms: Dyspnea • face swelling Clinical Procedure: — Specialty: Oncology Objective: Unknown etiology Background: Fibrosing mediastinitis (FM) is a rare, fibroproliferative disorder within the mediastinum. It is extremely rare for hematologic malignancies to develop as FM. Case Report: A 32-year-old Japanese man with a 1-month history of headache and 2-week history of facial swelling underwent chest computed tomography (CT); a diffuse mass-like lesion was revealed in the anterior mediastinum with severe stenosis of vital mediastinal organs. After a surgical biopsy, an initial diagnosis of idiopathic FM was made. The FM lesions responded mildly to corticosteroids but recurred repeatedly. Sixteen months after the treatment initiation, blasts appeared in the peripheral blood (PB), and the patient was diagnosed with B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL). Chemotherapy led to complete remission of the B-ALL/LBL and almost complete disappearance of FM-like lesions. Immunohistochemistry of the mediastinal biopsy specimen taken before the blasts’ appearance in PB demonstrated a CD34/CD7/terminal deoxynucleotidyl transferase-positive population, an identical pattern of expression common to the blasts in the patient’s PB and bone marrow. Conclusions: This is the first case report of B-ALL/LBL presenting as FM. This case underscores the importance of considering the possibility of latent hematologic malignancy even in the absence of new symptoms other than those caused by FM lesions for a long period of time. This is the first demonstration that leukemia cells may be present in the FM lesions from the initial stage of disease onset. Even if a diagnosis of idiopathic FM is confirmed, continued suspicion of the presence of hematologic malignancy is vital for improving patient outcomes.
DOI： 10.12659/AJCR.945804
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Chiba N., Suzuki S., Enriquez-Vera D., Utsunomiya A., Kubuki Y., Hidaka T., Shimoda K., Nakahata S., Yamada T., Morishita K.
Heliyon 10 ( 20 ) e38507 2024年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Heliyon
Adult T-cell leukemia/lymphoma (ATLL) is a refractory blood cancer with severe immunodeficiency resulting from retroviral infection. ATLL develops in only 5 % of HTLV-1-infected individuals, but the entire mechanism of ATLL progression remains unknown. Since recent studies have reported that the gut microbiome influences the progression of various diseases, we hypothesized that ATLL is also related to the gut microbiome and aimed to investigate this relationship. We analyzed the taxonomic and functional profiles of the gut microbiota of ATLL patients (n = 28) and HTLV-1-infected individuals (n = 37). We found that the succinic semialdehyde (SSA) synthesis pathway was significantly enriched in the gut microbiome of ATLL patients (P = 0.000682), and Klebsiella, whose abundance was significantly greater in ATLL patients and high-risk HTLV-1-infected individuals (P = 0.0326), was the main contributor to this pathway. Administration of SSAs to ATLL cell lines resulted in significant cell proliferation. Herein, we propose that the gut microbiome can regulate ATLL progression via metabolites.
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Sugimoto Y, Nagaharu K, Ohya E, Ohishi K, Tawara I, Ito T, Gotoh A, Nakamae M, Kimura F, Koike M, Kirito K, Wada H, Usuki K, Tanaka T, Mori T, Wakita S, Saito TI, Saito AM, Shimoda K, Kurokawa T, Tomita A, Edahiro Y, Hashimoto Y, Kiyoi H, Akashi K, Matsumura I, Takenaka K, Komatsu N
International journal of hematology 120 ( 6 ) 684 - 693 2024年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
We report the first large-scale retrospective cohort study on adolescent and young adult (AYA) polycythemia vera (PV) and essential thrombocythemia (ET) in Japan, a subgroup analysis using Japanese multicenter registry data (JSH-MPN-R18). This study included patients with PV (n = 31) or ET (n = 141) aged 20 to 39 years at the initial visit. Hemorrhage-free survival (HFS) was better in AYA ET than in non-AYA ET (5-year HFS: 100% vs. 88.6%, p < 0.01), which might be attributed to differences in antithrombotic treatment rates between AYA and non-AYA patients. Although thrombosis-free survival did not differ statistically, the percentage of venous thrombotic events (TEs) among total TEs was higher in AYA compared to non-AYA PV and ET in Japan (26.0% vs. 6.0%, p < 0.01), but much lower than figures reported in European or US cohorts. Cytoreductive therapy (CRT) was administered to 25.8% of AYA patients with PV and 43.3% of AYA patients with ET, and the reason was usually unrelated to high risk of thrombosis. These results could be used to develop a more appropriate strategy for managing PV and ET in the Japanese AYA population.
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Nagaharu K., Ohya E., Edahiro Y., Hashimoto Y., Ito T., Gotoh A., Nakamae M., Kimura F., Koike M., Kirito K., Wada H., Usuki K., Tanaka T., Mori T., Wakita S., Saito T.I., Saito A.M., Shimoda K., Kurokawa T., Tomita A., Kiyoi H., Akashi K., Matsumura I., Takenaka K., Komatsu N., Ohishi K., Tawara I., Sugimoto Y.
Annals of Hematology 103 ( 10 ) 4349 - 4350 2024年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Annals of Hematology
In the published paper, it was observed that a portion of Supplementary Figure 1 is highlighted in red and Supplementary Figure 2 lacks the figures. The original article has been corrected.
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Abu-Zeinah G., Qin A., Gill H., Komatsu N., Mascarenhas J., Shih W.J., Zagrijtschuk O., Sato T., Shimoda K., Silver R.T., Mesa R.
Annals of Hematology 103 ( 9 ) 3573 - 3583 2024年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Annals of Hematology
Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with “early/lower-risk PMF”, defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.
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Nagaharu K., Ohya E., Edahiro Y., Hashimoto Y., Ito T., Gotoh A., Nakamae M., Kimura F., Koike M., Kirito K., Wada H., Usuki K., Tanaka T., Mori T., Wakita S., Saito T.I., Saito A.M., Shimoda K., Kurokawa T., Tomita A., Kiyoi H., Akashi K., Matsumura I., Takenaka K., Komatsu N., Ohishi K., Tawara I., Sugimoto Y.
Annals of Hematology 103 ( 9 ) 3535 - 3541 2024年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Annals of Hematology
Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch’s T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.
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Shimoda K., Komatsu N., Matsumura I., Ikeda K., Hino M., Hidaka M., Maeda Y., Kondo T., Fujisaki T., Shoshi K., Azuma K., Fukushima R., Kawashima J., Kosugi H.
International Journal of Hematology 120 ( 3 ) 314 - 324 2024年9月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
Momelotinib, an oral Janus kinase (JAK) 1/2 and activin A receptor type 1 inhibitor, improved symptoms, splenomegaly, and anemia in patients with myelofibrosis (MF). This sub-analysis of SIMPLIFY-1 evaluated the efficacy and safety of momelotinib versus ruxolitinib in Japanese patients with JAK inhibitor (JAKi)-naïve MF. Patients were randomized 1:1 to receive momelotinib 200 mg once daily or ruxolitinib 20 mg twice daily (or modified based on label) for 24 weeks, after which patients could receive open-label momelotinib. The primary endpoint was splenic response rate (SRR; ≥ 35% reduction in spleen volume) at 24 weeks; main secondary endpoints were total symptom score (TSS) response (≥ 50% reduction) and transfusion independence (TI) rates. Fifteen Japanese patients (momelotinib, n = 6; ruxolitinib, n = 9) were enrolled; all completed treatment. At Week 24, SRR was 50.0% with momelotinib and 44.4% with ruxolitinib. TSS response rates were 33.3% and 0%, and TI rates were 83.3% and 44.4%. Any-grade treatment-related adverse event (TRAE) rates were 83.3% with momelotinib and 88.9% with ruxolitinib. Grade 3/4 TRAE rates were 0% and 55.6%, with specific events being anemia (55.6%) and vertigo (11.1%) with ruxolitinib. Momelotinib was well tolerated, improved spleen and symptom responses, and reduced transfusion requirements in Japanese patients with JAKi-naïve MF.
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Watanuki S., Kobayashi H., Sugiura Y., Yamamoto M., Karigane D., Shiroshita K., Sorimachi Y., Morikawa T., Fujita S., Shide K., Haraguchi M., Tamaki S., Mikawa T., Kondoh H., Nakano H., Sumiyama K., Nagamatsu G., Goda N., Okamoto S., Nakamura-Ishizu A., Shimoda K., Suematsu M., Suda T., Takubo K.
Cell Stem Cell 31 ( 8 ) 1145 - 1161.e15 2024年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cell Stem Cell
Aging generally predisposes stem cells to functional decline, impairing tissue homeostasis. Here, we report that hematopoietic stem cells (HSCs) acquire metabolic resilience that promotes cell survival. High-resolution real-time ATP analysis with glucose tracing and metabolic flux analysis revealed that old HSCs reprogram their metabolism to activate the pentose phosphate pathway (PPP), becoming more resistant to oxidative stress and less dependent on glycolytic ATP production at steady state. As a result, old HSCs can survive without glycolysis, adapting to the physiological cytokine environment in bone marrow. Mechanistically, old HSCs enhance mitochondrial complex II metabolism during stress to promote ATP production. Furthermore, increased succinate dehydrogenase assembly factor 1 (SDHAF1) in old HSCs, induced by physiological low-concentration thrombopoietin (TPO) exposure, enables rapid mitochondrial ATP production upon metabolic stress, thereby improving survival. This study provides insight into the acquisition of resilience through metabolic reprogramming in old HSCs and its molecular basis to ameliorate age-related hematopoietic abnormalities.
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Shimoda K., Qin A., Komatsu N., Kirito K.
International Journal of Hematology 120 ( 2 ) 151 - 156 2024年8月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal erythrocytosis. A phase 2 study reported that ropeginterferon alfa-2b is a well-tolerated and effective treatment for PV in Japanese patients. This post hoc analysis of the phase 2 data further evaluated outcomes in patients at low risk of thrombosis (low-risk PV). Among 20 patients with low-risk PV, 60.0% (12/20) and 85.0% (17/20) achieved < 45% hematocrit by weeks 24 and 52, respectively. The proportion of responders with complete hematologic response (CHR) was 60.0% (12/20) at week 52, and the median time to response was 11.9 months. The mean JAK2 V617F allele burden decreased from 75.8% at baseline to 53.7% at week 52. No patient experienced thrombosis or bleeding episodes. All patients experienced treatment-emergent adverse events (TEAEs) related to ropeginterferon alfa-2b, but no grade ≥ 3 TEAEs or deaths related to ropeginterferon alfa-2b occurred, and no new safety concerns arose. This analysis indicated that ropeginterferon alfa-2b may be an effective treatment option for Japanese patients with low-risk PV.
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Ropeginterferon alfa-2b shows anti-polycythaemia vera activity without causing clinically significant anaemia. 査読あり
Kirito K, Qin A, Suo S, Fu R, Wu D, Sato T, Zagrijtschuk O, Shimoda K, Komatsu N, Jin J
BJC reports 2 ( 1 ) 51 2024年7月
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Uchida T., Ueno H., Sekishima A., Sekishima H., Konagata A., Nakamura T., Kogo F., Nabekura H., Tanaka Y., Shimizu K., Yamaguchi H., Shimoda K.
Diabetology International 15 ( 3 ) 439 - 446 2024年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Diabetology International
Aim: Education on insulin self-injection techniques is important for good glycemic control, but its effectiveness in some elderly patients is limited due to loss of cognitive function and impaired activities of daily living. We hypothesized that classification using the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) would help identify elderly patients with diabetes who effectively learn self-injection techniques. Methods: Diabetes patients aged ≥ 65 years who used a self-injection insulin pen were administered the DASC-8 and a questionnaire to evaluate insulin self-injection techniques, and then received technical education. The questionnaire was administered again 4 months later, and patients were classified into the education-effective and education-ineffective groups. The achievement of HbA1c targets defined for each patient according to guidelines based on DASC-8 category was examined over 12 months. Results: 76 Japanese patients (median age 72.0 years and 53.9% female) with DASC-8 categories I (n = 55), II (n = 13), and III (n = 8) were enrolled. In the education-effective group, the percentage of patients in category I was significantly higher than that of patients in category II or III (92.0% to 23.8%, P < 0.001). Category I was independently associated with education effectiveness (odds ratio 14.50, 95% confidence interval: 2.110–100.0, P = 0.007). Category I patients in the education-effective group showed significantly improved achievement of target HbA1c from baseline to the 12th month (from 27.6% to 62.1%, P = 0.008). Conclusions: The DASC-8 was a useful indicator for identifying elderly patients who would benefit from education on self-injection techniques.
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Usuki K., Kameda T., Kawano N., Ito T., Hashimoto Y., Shide K., Kawano H., Sekine M., Toyama T., Iizuka H., Sato S., Takeuchi M., Ishizaki J., Maeda K., Nakai M., Yamashita K., Kubuki Y., Shimoda K.
International Journal of Hematology 119 ( 6 ) 722 - 727 2024年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
Myeloid and lymphoid neoplasms associated with FGFR1 abnormalities (MLN-FGFR1 abnormalities) are rare hematologic malignancies associated with chromosome 8p11.2 abnormalities. Translocations of 8p11.2 were detected in 10 of 17,039 (0.06%) unique patient cytogenetic studies performed at nine institutions in Japan. No inversions or insertions of 8p11.2 were detected. Among the 10 patients with 8p11.2 translocations, three patients were diagnosed with MLN-FGFR1 abnormalities, which were confirmed by FISH analysis. Peripheral blood eosinophilia was observed in all three patients, and all progressed to AML or T-lymphoblastic lymphoma/leukemia. The prevalence of 8p11.2 translocations in clinical practice and the proportion of MLN-FGFR1 abnormalities in patients with 8p11.2 translocations in Japan were consistent with those in previous reports from Western countries.
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Ichikawa T., Suekane A., Nakahata S., Iha H., Shimoda K., Murakami T., Morishita K.
International Journal of Molecular Sciences 25 ( 5 ) 2842 2024年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Molecular Sciences
N-myc downstream-regulated gene 2 (NDRG2), which is a tumour suppressor, is frequently lost in many types of tumours, including adult T-cell leukaemia/lymphoma (ATL). The downregulation of NDRG2 expression is involved in tumour progression through the aberrant phosphorylation of several important signalling molecules. We observed that the downregulation of NDRG2 induced the translocation of protein arginine methyltransferase 5 (PRMT5) from the nucleus to the cytoplasm via the increased phosphorylation of PRMT5 at Serine 335. In NDRG2low ATL, cytoplasmic PRMT5 enhanced HSP90A chaperone activity via arginine methylation, leading to tumour progression and the maintenance of oncogenic client proteins. Therefore, we examined whether the inhibition of PRMT5 activity is a drug target in NDRG2low tumours. The knockdown of PRMT5 and binding partner methylsome protein 50 (MEP50) expression significantly demonstrated the suppression of cell proliferation via the degradation of AKT and NEMO in NDRG2low ATL cells, whereas NDRG2-expressing cells did not impair the stability of client proteins. We suggest that the relationship between PRMT5/MEP50 and the downregulation of NDRG2 may exhibit a novel vulnerability and a therapeutic target. Treatment with the PRMT5-specific inhibitors CMP5 and HLCL61 was more sensitive in NDRG2low cancer cells than in NDRG2-expressing cells via the inhibition of HSP90 arginine methylation, along with the degradation of client proteins. Thus, interference with PRMT5 activity has become a feasible and effective strategy for promoting cancer vulnerability in NDRG2low ATL.
DOI： 10.3390/ijms25052842
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Mine K., Nagafuchi S., Akazawa S., Abiru N., Mori H., Kurisaki H., Shimoda K., Yoshikai Y., Takahashi H., Anzai K.
Nature Communications 15 ( 1 ) 1337 2024年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Nature Communications
Tyrosine kinase 2 (TYK2), a member of the JAK family, has attracted attention as a potential therapeutic target for autoimmune diseases. However, the role of TYK2 in CD8+ T cells and autoimmune type 1 diabetes (T1D) is poorly understood. In this study, we generate Tyk2 gene knockout non-obese diabetes (NOD) mice and demonstrate that the loss of Tyk2 inhibits the development of autoreactive CD8+ T-BET+ cytotoxic T lymphocytes (CTLs) by impairing IL-12 signaling in CD8+ T cells and the CD8+ resident dendritic cell-driven cross-priming of CTLs in the pancreatic lymph node (PLN). Tyk2-deficient CTLs display reduced cytotoxicity. Increased inflammatory responses in β-cells with aging are dampened by Tyk2 deficiency. Furthermore, treatment with BMS-986165, a selective TYK2 inhibitor, inhibits the expansion of T-BET+ CTLs, inflammation in β-cells and the onset of autoimmune T1D in NOD mice. Thus, our study reveals the diverse roles of TYK2 in driving the pathogenesis of T1D.
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Mesa R, Verstovsek S, Platzbecker U, Gupta V, Lavie D, Giraldo P, Recher C, Kiladjian JJ, Oh ST, Gerds AT, Devos T, Passamonti F, Vannucchi AM, Egyed M, Lech-Maranda E, Pluta A, Nilsson L, Shimoda K, McLornan D, Kawashima J, Klencke B, Huang M, Strouse B, Harrison C
Haematologica 109 ( 2 ) 676 - 681 2024年2月
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Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers. 査読あり
Kameda T., Utsunomiya A., Otsuka N., Kubuki Y., Uchida T., Shide K., Kamiunten A., Nakano N., Tokunaga M., Miyazono T., Ito Y., Yonekura K., Kawakita T., Akizuki K., Tahira Y., Karasawa M., Hidaka T., Konagata A., Taniguchi N., Nagatomo Y., Kogo F., Shimizu K., Ueno H., Ishizaki J., Takahashi N., Ikei Y., Hidaka M., Yamaguchi H., Shimoda K.
BMC Infectious Diseases 24 ( 1 ) 96 2024年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Infectious Diseases
Background: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. Methods: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. Results: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. Conclusions: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
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Shide K., Takenaka K., Kitanaka A., Numata A., Kameda T., Yamauchi T., Inagaki A., Mizuno S., Takami A., Ito S., Hagihara M., Usuki K., Maekawa T., Sunami K., Ueda Y., Tsutsui M., Ando M., Komatsu N., Ozawa K., Kurokawa M., Arai S., Mitani K., Akashi K., Shimoda K.
Annals of Hematology 103 ( 1 ) 97 - 103 2024年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Annals of Hematology
There are few prospective studies on patients with post-essential thrombocythemia myelofibrosis (PET-MF) and post-polycythemia vera myelofibrosis (PPV-MF). Therefore, we conducted a nationwide longitudinal prospective survey to clarify the clinical characteristics of these diseases. A total of 197 PET-MF and 117 PPV-MF patients diagnosed between 2012 and 2021 were analyzed. The median age at diagnosis was 70.0 years for both diseases. The time from diagnosis of ET or PV to that of MF was 9.6 and 10.4 years, respectively, with no significant difference. Patients with PPV-MF had higher hemoglobin levels and white blood cell counts than those with PET-MF, whereas those with PET-MF had higher platelet counts than those with PPV-MF. Although splenomegaly was more frequent in patients with PPV-MF at diagnosis, there was no difference in the frequency of constitutional symptoms. Ruxolitinib was the most common treatment administered to 74.6% and 83.8% of patients with PET-MF and PPV-MF, respectively. Patients with PET-MF and PPV-MF had similar prognoses, with 3-year overall survival (OS) of 0.742 in PET-MF and 0.768 in PPV-MF patients. In both diseases, leukemic transformation was the leading cause of death, followed by infection. The 3-year OS for patients with PET/PPV-MF and primary MF diagnosed during the same period was 0.754 and 0.626, respectively, with no significant difference. This survey provides real-world clinical features and prognostic data on secondary myelofibrosis in the ruxolitinib era.
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Edahiro Y., Kirito K., Gotoh A., Takenaka K., Sugimoto Y., Komatsu N., Shimoda K.
Hematology 28 ( 1 ) 2227817 2023年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hematology (United Kingdom)
Objectives: This Japanese cross-sectional survey evaluated the symptoms, daily living activities, and treatment needs of patients with polycythemia vera (PV), as perceived by patients themselves and their physicians. Methods: The study was conducted at 112 centers (March to July 2022) and included PV patients aged ≥20 years (n = 265) and their attending physicians (n = 151). The patient and physician questionnaires included 34 and 29 questions, respectively, to assess daily living, PV symptoms, treatment goals, and physician-patient communication. Results: Concerning daily living (primary endpoint), work (13.2%), leisure activities (11.3%), and family life (9.6%) were most affected by PV symptoms. Patients aged <60 years more frequently reported an impact on daily living than patients aged ≥60 years. Some patients (30%) reported anxiety about their future condition. The most common symptoms were pruritus (13.6%) and fatigue (10.9%). Pruritus was ranked as the first treatment need for patients, while physicians ranked it fourth. Concerning treatment goals, physicians prioritized thrombosis/vascular event prevention, while patients prioritized delaying PV progression. Physicians were less satisfied with physician-patient communication than patients. Conclusions: Patients’ daily living was largely affected by PV symptoms. There are differences in physician and patient perceptions of symptoms, daily living, and treatment needs in Japan. Trial registration: UMIN Japan identifier: UMIN000047047.
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Kawano N., Kyohei Y., Miyoshi H., Yoshida N., Ohshima K., Arakawa F., Nakashima K., Kameda T., Kogure Y., Ito Y., Yoshida S., Kuriyama T., Nakaike T., Tochigi T., Takigawa K., Yamashita K., Toyofuku A., Manabe T., Doi A., Terasaka S., Marutsuka K., Ochiai H., Kikuchi I., Mori Y., Kataoka K., Yoshizumi T., Yamauchi J., Yamano Y., Shimoda K.
Renal Replacement Therapy 9 ( 1 ) 2023年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Renal Replacement Therapy
Backgrounds: Therefore, reports on the risk of HTLV-1-related diseases in organ transplantation have increased in recent years, and the management of HTLV in renal transplantation remains a challenge. Patients and methods: We retrospectively analyzed four HTLV-1-positive recipients or donors among 89 renal transplantation cases from 2006 to 2021. Results: Among the four HTLV-1-positive recipients, two patients developed adult T cell leukemia/lymphoma (ATL) derived from recipients at approximately 3 years (1016 days and 1195 days) after renal transplantation. Case 1 developed lymphoma-type ATL (an extranodal primary cutaneous variant), including skin and pulmonary lesions. The patient achieved CR with FK tapering and CHOP therapy following cord blood stem cell transplantation. However, the patient died 101 days after ATL development because of a severe fungal infection. Case 2 developed acute-type ATL with an unusual phenotype of CD4+8+30+. The patient was treated with FK tapering and palliative therapy because of poor PS. Notably, in case 1, histopathological findings showed high numbers of PD-1-positive TIL cells in ATL, suggesting exhausted T cells and a correlation with the early onset of ATL. Furthermore, in Case 2, histopathological findings revealed CD 30 expression in ATL cells, suggesting the importance of CD 30 in ATL development. Importantly, case 2 showed typical driver mutations, including CCR4 truncation mutations of the C-terminal, TBL1XR1 mutation, and TP53 mutation in the splice site. Notably, our present study and our previous study on renal transplantation strongly indicated that two out of two and one out of 59 “recipient” positive cases developed ATL, respectively. Furthermore, our previous nationwide study 4 out of 10 “donor” positive cases developed HAM. These findings showed that ATL may be derived from HTLV-I+ recipient cells and HAM may be derived from HTLV-1+ donor cells, although the precise mechanism remains unknown. Conclusions: Thus, early onset and rapid progression of ATL with poor outcomes should be considered in HTLV-1 endemic areas. Furthermore, immunological or genetic mechanisms may be related to the development of ATL after renal transplantation. We believe that the mechanism of onset of ATL after transplantation may be important when considering the immune environment of ATL itself.
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Uchida T, Yamaguchi H, Arimura Y, Nagayama A, Moritaka K, Inoguchi Y, Ashida K, Nomura M, Nakazato M, Shimoda K
Endocrine journal 78 ( 8 ) 825 - 832 2023年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本内分泌学会
There is no computed tomography (CT)-based numerical index for predicting Cushing’s syndrome (CS) in patients with adrenal incidentalomas. We tested the hypothesis that the iliopsoas muscle (Ip-M) to visceral fat (V-fat) ratio (IVR) on CT may predict CS in elderly female patients with adrenal tumors. We examined the V-fat area, subcutaneous fat (S-fat) area, Ip-M area, V-fat/S-fat ratio, and IVR at the third lumbar vertebra (L3) level using abdominal CT in female patients aged ≥50 years with cortisol-producing adrenal tumor diagnosed with CS or non-functioning adrenal tumor (NFT) in the derivation cohort. We performed receiver operating characteristic (ROC) analysis to evaluate the diagnostic value of the V-fat/S-fat ratio and IVR for predicting CS. We assessed the usefulness of the IVR in a separate validation cohort. In the derivation cohort, the IVR was significantly lower in the 9 patients with CS than in the 15 patients with NFT (<i>p</i> < 0.001). In ROC analysis with a cut-off value of 0.067, the IVR showed a sensitivity of 100%, specificity of 80.0%, positive likelihood ratio (PLR) of 5.000, and negative likelihood ratio (NLR) of 0.000. The area under the curve was significantly higher for the IVR than for the V-fat/S-fat ratio (0.933 <i>vs.</i> 0.704, respectively, <i>p</i> = 0.036). In 23 patients in the validation cohort, the IVR demonstrated a PLR of 5.714 and an NLR of 0.327. The novel IVR index, based on single-slice CT at the L3 level, predicted CS in elderly female patients with adrenal tumors.
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Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma. 査読あり
Kameda T, Kataoka K, Kamiunten A, Hidaka M, Miyoshi H, Nakano N, Nosaka K, Yoshimitsu M, Yasunaga JI, Kogure Y, Shide K, Miyahara M, Sakamoto T, Akizuki K, Hidaka T, Kubuki Y, Koya J, Kawano N, Yamashita K, Kawano H, Toyama T, Maeda K, Marutsuka K, Imaizumi Y, Kato K, Sugio T, Tokunaga M, Tashiro Y, Takaori-Kondo A, Miyazaki Y, Akashi K, Ishitsuka K, Matsuoka M, Ohshima K, Watanabe T, Kitanaka A, Utsunomiya A, Ogawa S, Shimoda K
Haematologica 108 ( 8 ) 2178 - 2191 2023年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Ferrata Storti Foundation (Haematologica)
The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3).
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Nationwide prospective survey of secondary myelofibrosis in Japan: superiority of DIPSS-plus to MYSEC-PM as a survival risk model. 査読あり
Shide K, Takenaka K, Kitanaka A, Numata A, Kameda T, Yamauchi T, Inagaki A, Mizuno S, Takami A, Ito S, Hagihara M, Usuki K, Maekawa T, Sunami K, Ueda Y, Tsutsui M, Ando M, Komatsu N, Ozawa K, Kurokawa M, Arai S, Mitani K, Akashi K, Shimoda K
Blood cancer journal 13 ( 1 ) 110 2023年7月
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Kawano N., Shimonodan H., Nagahiro Y., Yoshida S., Kuriyama T., Takigawa K., Tochigi T., Nakaike T., Makino S., Yamashita K., Marutsuka K., Ochiai H., Mori Y., Shimoda K., Ohshima K., Mashiba K., Kikuchi I.
Journal of Clinical and Experimental Hematopathology 63 ( 2 ) 73 - 82 2023年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical and Experimental Hematopathology
Recently, the ratio of C-reactive protein to albumin (CAR) is used as an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in solid tumors and hematological malignancy. However, no studies of the CAR have been performed in patients with adult T-cell leukemia-lymphoma (ATL). We retrospectively analyzed the clinical features and outcomes in 68 newly diagnosed acute-and lymphoma-type ATL [(acute-(n=42) or lymphoma-type (n=26)] patients in Miyazaki Prefecture from 2013 to 2017. Furthermore, we investigated correlations between pretreatment CAR levels and clinical features. The median age was 67 years (range, 44-87). Patients were initially treated by either palliative therapy (n=14) or chemotherapy [n=54; CHOP therapy (n=37)/ VCAP-AMP-VECP therapy (n=17)], and showed median survival durations of 0.5 months and 7.4 months, respectively. The factors affecting OS by multivariate analysis were age, BUN, and CAR. Importantly, we revealed that the high CAR group (optimal cut-off point; 0.553) was a significant indicator of worse OS by multivariate analysis (p< 0.001, HR; 5.46). The median survival of patients with a CAR< 0.553 was 8.37 months, while patients with a CAR>0.553 had a median survival of 3.94 months. The different clinical features between high CAR and low CAR groups were hypoproteinemia and the implementation of chemotherapy. Furthermore, in the chemotherapy group, but not the palliative therapy group, CAR was a significant prognostic marker. Our study indicated that CAR may be a new simple and significant independent prognostic marker in acute-and lymphoma-type ATL patients.
DOI： 10.3960/jslrt.22039
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Association between personality traits and glycemic control after inpatient diabetes education. 査読あり
Uchida T, Ueno H, Konagata A, Nakamura T, Taniguchi N, Nabekura H, Kogo F, Nagatomo Y, Tanaka Y, Shimizu K, Shiiya T, Yamaguchi H, Shimoda K
Metabolism open 18 100244 2023年6月
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A Response to Letter to the Editor: Can Imeglimin Improve the Systolic Time Intervals in Diabetes Mellitus? 査読あり
Uchida T,Ueno H, Konagata A, Taniguchi N, Kogo F, Nagatomo Y, Shimizu K, Yamaguchi H, Shimoda K.
Diabetes Therapy 14 ( 6 ) 1075 - 1076 2023年6月
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Uchida T, Ueno H, Konagata A, Taniguchi N, Kogo F, Nagatomo Y, Shimizu K, Yamaguchi H, Shimoda K
Diabetes therapy : research, treatment and education of diabetes and related disorders 14 ( 3 ) 569 - 579 2023年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Diabetes Therapy
Introduction: Endothelial dysfunction is a risk factor for cardiovascular disease in patients with diabetes. We hypothesized that imeglimin, a novel oral hypoglycemic agent, would improve endothelial function. Methods: In this study, imeglimin was administered to patients with type 2 diabetes and HbA1c ≥ 6.5% who were not receiving insulin therapy. A meal tolerance test (592 kcal, glucose 75.0 g, fat 28.5 g) was performed before and 3 months after administration, and endothelial function, blood glucose, insulin, glucagon, and triglycerides were evaluated. Endothelial function was assessed by flow-mediated dilation (FMD). Results: Twelve patients (50% male) with a median age of 55.5 years old (interquartile range [IQR] 51.3–66.0) were enrolled. Fasting FMD did not differ before or 3 months after imeglimin administration (from 6.1 [3.9–8.5] to 6.6 [3.9–9.0], p = 0.092), but 2 h postprandial FMD was significantly improved 3 months after imeglimin administration (from 2.3 [1.9–3.4] to 2.9 [2.4–4.7], p = 0.013). In terms of the glucose profile, imeglimin administration significantly improved HbA1c (from 7.2 ± 0.6% to 6.9 ± 0.6%, p = 0.007), fasting glucose (from 138 ± 19 mg/dL to 128 ± 20 mg/dL, p = 0.020), and 2 h postprandial glucose (from 251 ± 47 mg/dL to 215 ± 68 mg/dL, p = 0.035). The change in 2 h postprandial FMD between before and 3 months after imeglimin administration (Δ2 h postprandial FMD) was negatively correlated with Δ2 h postprandial glucose (r = − 0.653, p = 0.021) in a univariate correlation coefficient analysis. Both patients with and without decreased postprandial glucose 3 months after imeglimin administration had improved postprandial FMD. Conclusion: In this small study, imeglimin administration improved 2 h postprandial FMD. Both glycemic control-dependent and -independent mechanisms might contribute to improved endothelial function. Trial Registration: This research was registered in the University Hospital Medical Information Network (UMIN, UMIN000046311).
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Kameda T., Shide K., Kamiunten A., Kogure Y., Morishita D., Koya J., Tahira Y., Akizuki K., Yokomizo-Nakano T., Kubota S., Marutsuka K., Sekine M., Hidaka T., Kubuki Y., Kitai Y., Matsuda T., Yoda A., Ohshima T., Sugiyama M., Sashida G., Kataoka K., Ogawa S., Shimoda K.
Communications Biology 5 ( 1 ) 1309 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Communications Biology
Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1). In addition to HTLV-1 bZIP factor (HBZ), a leukemogenic antisense transcript of HTLV-1, abnormalities of genes involved in TCR-NF-κB signaling, such as CARD11, are detected in about 90% of patients. Utilizing mice expressing CD4+ T cell-specific CARD11(E626K) and/or CD4+ T cell-specific HBZ, namely CARD11(E626K)CD4-Cre mice, HBZ transgenic (Tg) mice, and CARD11(E626K)CD4-Cre;HBZ Tg double transgenic mice, we clarify these genes’ pathogenetic effects. CARD11(E626K)CD4-Cre and HBZ Tg mice exhibit lymphocytic invasion to many organs, including the lungs, and double transgenic mice develop lymphoproliferative disease and increase CD4+ T cells in vivo. CARD11(E626K) and HBZ cooperatively activate the non-canonical NF-κB pathway, IRF4 targets, BATF3/IRF4/HBZ transcriptional network, MYC targets, and E2F targets. Most KEGG and HALLMARK gene sets enriched in acute-type ATL are also enriched in double transgenic mice, indicating that these genes cooperatively contribute to ATL development.
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Kawano N., Abe T., Ikeda N., Nagahiro Y., Kawano S., Tochigi T., Nakaike T., Yamashita K., Kubo K., Yamanaka A., Terasaka S., Marutsuka K., Mashiba K., Kikuchi I., Shimoda K., Matsumoto M., Ochiai H.
Renal Replacement Therapy 8 ( 1 ) 2022年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Renal Replacement Therapy
Background: Although atypical hemolytic uremic syndrome (aHUS) is a life-threatening clinical entity that was characterized by thrombotic microangiopathy (TMA) with the activation of the complement system and the efficient treatment of eculizumab, the clinical features of aHUS have been unclear because of the rare incidence. Case presentation: We retrospectively analyzed 4 aHUS cases at a single institution during 2015–2019. Here, we presented 4 aHUS cases with renal transplantation (one case), influenza/acute interstitial pneumonia/disseminated intravascular coagulation (two cases), and severe fever with thrombocytopenia syndrome (one case), respectively. Initial clinical symptoms were microangiopathic hemolytic anemia (four cases), renal dysfunction (four cases), thrombocytopenia (four cases), and pulmonary hemorrhage (three cases) consisted with TMA features. Subsequent further examinations ruled out thrombotic thrombocytopenic purpura, Shiga toxin-producing E.coli-induced hemolytic uremic syndrome, and secondary TMA. Taken these findings together, we made the clinical diagnosis of aHUS. Furthermore, all cases also presented the high levels of plasma soluble C5b-9 (871.1 ng/ml, 1144.3 ng/ml, 929.2 ng/ml, and 337.5 ng/ml), suggesting persistent activation of complementary system. Regarding the treatment, plasma exchange (PE) (four cases) and eculizumab (two cases) therapy were administered for aHUS cases. Consequently, case 2 and case 4 were still alive with 768 days and 235 days, respectively. The other two cases were dead at 34 days and 13 days, respectively. Finally, although the previous reported genetic pathogenetic mutations were not detected in our cases, multiple genetic variants of complement factors were detected as CFH (H402Y, E936D), and THBD (A473V) in case 1, CFH (V62I, H402Y, V837I) in case 2, and CFH (H402Y, E 936D) and THBD (A473V) in case 3, CFH (V62I, H402Y, E936D) and THBD (473V) in case 4, respectively. Conclusions: Because of still high mortality in our study, an urgent diagnosis of aHUS and subsequent immediate treatment including PE and eculizumab should be essential in clinical practice. Furthermore, the multiple genetic variants and the triggers may be related to one of the pathogenesis of aHUS. Thus, we assume that such a case-oriented study would be highly useful to the physicians who directly care for aHUS cases in clinical practice.
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Edahiro Y., Ito T., Gotoh A., Nakamae M., Kimura F., Koike M., Kirito K., Wada H., Usuki K., Tanaka T., Mori T., Wakita S., Saito T.I., Kada A., Saito A.M., Shimoda K., Sugimoto Y., Kurokawa T., Tomita A., Hashimoto Y., Akashi K., Matsumura I., Takenaka K., Komatsu N.
International Journal of Hematology 116 ( 5 ) 696 - 711 2022年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
The presence of a JAK2 V617F or JAK2 exon 12 mutation is one of the three major criteria listed for the diagnosis of polycythemia vera (PV) in the 2017 World Health Organization Classification. However, a nationwide study has not yet been conducted in Japan since the discovery of JAK2 mutations. Therefore, the Japanese Society of Hematology (JSH) retrospectively analyzed the clinical characteristics of 596 Japanese patients with PV diagnosed between April 2005 and March 2018. Among the 473 patients with complete data on JAK2 mutations available, 446 (94.3%) and 10 (2.1%) were positive for the JAK2 V617F and JAK2 exon 12 mutations, respectively. During a median follow-up of 46 months (range: 0–179 months), 47 (7.9%) deaths occurred. The major causes of death were secondary malignancies (23.4%), acute leukemia (12.8%), non-leukemic progressive disease (10.6%) and thrombotic (6.4%) and hemorrhagic complications (6.4%). Thrombotic and hemorrhagic events occurred during the clinical course in 4.0% (n = 24) and 3.5% (n = 21) of patients, respectively. These results show that the international PV prognostic score (age, venous thrombosis and leukocytosis) is applicable to Japanese patients with PV.
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Correction to: Efficacy and safety of ropeginterferon alfa-2b in Japanese patients with polycythemia vera: an open-label, single-arm, phase 2 study. 査読あり
Edahiro Y, Ohishi K, Gotoh A, Takenaka K, Shibayama H, Shimizu T, Usuki K, Shimoda K, Ito M, VanWart SA, Zagrijtschuk O, Qin A, Kawase H, Miyachi N, Sato T, Komatsu N, Kirito K
International journal of hematology 116 ( 4 ) 642 - 643 2022年10月
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Kawano N, Nakamura S, Mochida K, Yoshida S, Kuriyama T, Nakaike T, Shimokawa T, Tochigi T, Yamashita K, Mashiba K, Kikuchi I, Takarabe A, Moriguchi S, Mori Y, Takenaka K, Shimoda K, Ochiai H, Amano M
Internal medicine (Tokyo, Japan) 61 ( 18 ) 2771 - 2774 2022年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本内科学会
Secondary malignancies that develop after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) have become serious issues. A 47-year-old man who developed acute myeloid leukemia in 2009 and subsequently underwent allo-HSCT twice: in 2009 and 2011. In 2015, voriconazole for lung aspergillus was started. In 2018, chronic graft-versus-host disease (GVHD) and multiple actinic keratoses manifested at his head. In 2020, some lesions were diagnosed as squamous cell carcinoma, so voriconazole was withdrawn, and subsequent surgery and radiation led to remission. Long-term administration of voriconazole in addition to allo-HSCT and chronic GVHD may be closely related to secondary skin cancer.
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Edahiro Y, Ohishi K, Gotoh A, Takenaka K, Shibayama H, Shimizu T, Usuki K, Shimoda K, Ito M, VanWart SA, Zagrijtschuk O, Qin A, Kawase H, Miyachi N, Sato T, Komatsu N, Kirito K
International journal of hematology 116 ( 2 ) 215 - 227 2022年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
Ropeginterferon alfa-2b is a novel, site-selective, monopegylated recombinant human interferon alfa-2b. Safety and efficacy of ropeginterferon alfa-2b for the treatment of polycythemia vera were demonstrated in clinical studies conducted in European countries, but clinical studies in Japanese patients are lacking. This phase 2, open-label, multicenter, single-arm study investigated the safety and efficacy of ropeginterferon alfa-2b in 29 Japanese patients with polycythemia vera including young patients and patients with low thrombosis risk who are difficult to receive guideline-based standard treatments. The primary outcome of durable complete hematologic response without phlebotomy at months 9 and 12 was achieved by 8/29 (27.6%) patients. The fastest complete hematologic response was observed at week 12. A corresponding reduction in the JAK2 V617F allele burden from baseline to 52 weeks was also observed (mean ± standard deviation = − 19.2% ± 22.6%). No new safety concerns were identified in Japanese patients when compared with previous studies of ropeginterferon alfa-2b in European populations; the most common treatment-related adverse events were alopecia (55.2%), fatigue (27.6%) and influenza-like illness (27.6%). Most treatment-related adverse events were mild or moderate, with none of grade ≥ 3. Ropeginterferon alfa-2b is a safe and efficacious treatment option in Japanese patients with polycythemia vera.
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Utsunomiya A, Izutsu K, Jo T, Yoshida S, Tsukasaki K, Ando K, Choi I, Imaizumi Y, Kato K, Kurosawa M, Kusumoto S, Miyagi T, Ohtsuka E, Sasaki O, Shibayama H, Shimoda K, Takamatsu Y, Takano K, Yonekura K, Makita S, Taguchi J, Gillings M, Onogi H, Tobinai K
Cancer Science 113 ( 8 ) 2778 - 2787 2022年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Science
This multicenter, prospective phase IIb trial evaluating the efficacy and safety of tucidinostat (HBI-8000) in patients with relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATLL) was undertaken in Japan. Eligible patients had R/R ATLL and had failed standard of care treatment with chemotherapy and with mogamulizumab. Twenty-three patients received tucidinostat 40 mg orally twice per week and were included in efficacy and safety analyses. The primary end-point was objective response rate (ORR) assessed by an independent committee. The ORR was 30.4% (95% confidence interval [CI], 13.2, 52.9]. Median progression-free survival was 1.7 months (95% CI, 0.8, 7.4), median duration of response was 9.2 months (95% CI, 2.6, not reached), and median overall survival was 7.9 months (95% CI, 2.3, 18.0). All patients experienced adverse events (AEs), which were predominantly hematologic and gastrointestinal. Incidence of grade 3 or higher AEs was 78.3%; most were laboratory abnormalities (decreases in platelets, neutrophils, white blood cells, and hemoglobin). Tucidinostat was well tolerated with AEs that could be mostly managed with supportive care and dose modifications. Tucidinostat is a meaningful treatment option for R/R ATLL patients; further investigation is warranted.
DOI： 10.1111/cas.15431
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Momelotinib reduces transfusion requirements in patients with myelofibrosis 査読あり
Mesa R., Oh S.T., Gerds A.T., Gupta V., Catalano J., Cervantes F., Devos T., Hus M., Kiladjian J.J., Lech-Maranda E., McLornan D., Palmer J., Platzbecker U., Treliński J., Shimoda K., Donahue R., D’Hollander K., Kowalski M., Verstovsek S.
Leukemia and Lymphoma 63 ( 7 ) 1718 - 1722 2022年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia and Lymphoma
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Oncogenic isoform switch of tumor suppressor BCL11B in adult T-cell leukemia/lymphoma 査読あり
Permatasari H.K., Nakahata S., Ichikawa T., Fauzi Y.R., Kiyonari H., Shide K., Kameda T., Shimoda K., Ono M., Taki T., Taniwaki M., Futakuchi M., Morishita K.
Experimental Hematology 111 41 - 49 2022年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Experimental Hematology
B-Cell leukemia/lymphoma 11B (BCL11B) is a transcription factor important for T-cell development and acts as a tumor suppressor gene in T-cell acute lymphoblastic leukemia. Here, we identified BCL11B as a candidate leukemia-associated gene in human T-cell leukemia virus type 1 (HTLV-1)-induced adult T-cell leukemia/lymphoma (ATLL). Interestingly, the short form lacking exon 3 (BCL11B/S) protein was more highly expressed than the full-length BCL11B (BCL11B/L) in leukemic cells from most of the ATLL patients, although expression ratios of BCL11B/L to BCL11B/S were almost equal in control CD4+ T cells. BCL11B/S and BCL11B/L exhibited distinct subcellular localization and differential effects on cellular growth; BCL11B/L expression exhibited nuclear localization and inhibited cell growth in ATLL cells, whereas BCL11B/S exhibited nucleocytoplasmic distribution and accelerated cell growth. Furthermore, BCL11B/S expression accelerated the development of T-cell leukemia/lymphomas in transgenic mice carrying HTLV-1/HBZ, a critical viral factor in leukemogenesis, whereas these phenotypes did not occur in the double transgenic mice carrying BCL11B/L and HTLV-1/HBZ. In HTLV-1-infected T-cell lines, BCL11B expression is downregulated by HTLV-1/Tax, a viral factor necessary at the early stage of leukemogenesis. These results suggest that downregulation of BCL11B/L expression and upregulation of BCL11B/S may contribute to the development and progression of ATLL.
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Uchida T., Yamaguchi H., Kawabata T., Tanaka H., Kawano F., Shimoda K.
Oxford Medical Case Reports 2022 ( 4 ) 155 - 158 2022年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Oxford Medical Case Reports
We present a female patient with autonomously functioning thyroid nodule (AFTN) and coexisting follicular thyroid carcinoma (FTC). At age 21, a left thyroid nodule was incidentally detected on computer tomography (CT) scan. At age 33, she had cervical compression and CT showed the left thyroid nodule had increased in size from 13 to 27 mm. Laboratory investigation showed subclinical hyperthyroidism with positive for anti-thyroid peroxidase antibody and normal level of serum thyroglobulin. Repeated fine needle aspiration cytology diagnosed with follicular neoplasm with Hashimoto's thyroiditis. At age 35, she presented with palpitations due to overt hyperthyroidism. The left thyroid nodule increased in diameter to 33 mm, and thyroid scintigraphy showed elevated uptake in the left thyroid nodule, indicating an AFTN. Thyroidectomy was performed, and the left thyroid nodule was pathologically diagnosed with FTC with capsular invasion. In this case, the longitudinal increase in AFTN size suggested FTC and led to thyroidectomy.
DOI： 10.1093/omcr/omac041
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Prognosis of Indolent Adult T-Cell Leukemia/Lymphoma 査読あり
Kameda T., Shide K., Tahira Y., Sekine M., Sato S., Ishizaki J., Takeuchi M., Akizuki K., Kamiunten A., Shimoda H., Toyama T., Maeda K., Yamashita K., Kawano N., Kawano H., Hidaka T., Yamaguchi H., Kubuki Y., Kitanaka A., Matsuoka H., Shimoda K.
Viruses 14 ( 4 ) 710 2022年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Viruses
A retrospective chart survey of the clinical features of indolent adult T-cell leukemia/lymphoma (ATL) was conducted in the Miyazaki Prefecture, Japan. This study enrolled 24 smoldering-type ATLs, 10 favorable chronic-type ATLs, and 20 unfavorable chronic-type ATLs diagnosed between 2010 and 2018. Among them, 4, 3, and 10 progressed to acute-type ATLs during their clinical course. The median survival time (MST) in smoldering-type ATL and favorable chronic-type ATL was not reached, and their 4-year overall survival (OS) was 73% and 79%, respectively. Compared with this, the prognosis of unfavorable chronic-type ATL was poor. Its MST was 3.32 years, and the 4-year OS was 46% (p = 0.0095). In addition to the three features that determine the unfavorable characteristics of chronic-type ATL, namely, increased lactate dehydrogenase, increased blood urea nitrogen, and decreased albumin, the high-risk category by the indolent ATL-Prognostic Index, which was defined by an increment of soluble interleukin-2 receptor (sIL2-R) of >6000 U/mL, could explain the poor prognosis in indolent ATL patients. The level of sIL-2R might be an indicator of the initiation of therapy for indolent ATL.
DOI： 10.3390/v14040710
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Ichikawa T., Sugamoto K., Matsuura Y., Kunitake H., Shimoda K., Morishita K.
Cancer Science 113 ( 4 ) 1406 - 1416 2022年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Science
We have previously reported that the proanthocyanidin (PAC) fraction of blueberry leaf extract (BB-PAC) inhibits the proliferation of HTLV-1-infected adult T-cell leukemia (ATL) by inducing apoptosis. In the present study, we further analyzed the structure of BB-PAC and elucidated the molecular mechanism underlying the inhibitory function of HTLV-1-infected and ATL cells. After hot water extraction with fractionation with methanol-acetone, BB-PAC was found to be concentrated in fractions 4 to 7 (Fr7). The strongest inhibition of ATL cell growth was observed with Fr7, which contained the highest BB-PAC polymerization degree of 14. The basic structure of BB-PAC is mainly B-type bonds, with A-type bonds (7.1%) and cinchonain I units as the terminal unit (6.1%). The molecular mechanism of cytotoxicity observed around Fr7 against ATL cells was the degradation of JAK1 to 3 and the dephosphorylation of STAT3/5, which occurs by proteasome-dependent proteolysis, confirming that PAC directly binds to heat shock protein 90 (HSP90). JAK degradation was caused by proteasome-dependent proteolysis, and we identified the direct binding of PAC to HSP90. In addition, the binding of cochaperone ATPase homolog 1 (AHA1) to HSP90, which is required for activation of the cofactor HSP90, was inhibited by BB-PAC treatment. Therefore, BB-PAC inhibited the formation of the HSP90/AHA1 complex and promoted the degradation of JAK protein due to HSP90 dysfunction. These results suggest that the highly polymerized PAC component from blueberry leaves has great potential as a preventive and therapeutic agent against HTLV-1-infected and ATL cells.
DOI： 10.1111/cas.15277
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Whole-genome landscape of adult T-cell leukemia/lymphoma 査読あり
Kogure Y., Kameda T., Koya J., Yoshimitsu M., Nosaka K., Yasunaga J.i., Imaizumi Y., Watanabe M., Saito Y., Ito Y., McClure M.B., Tabata M., Shingaki S., Yoshifuji K., Chiba K., Okada A., Kakiuchi N., Nannya Y., Kamiunten A., Tahira Y., Akizuki K., Sekine M., Shide K., Hidaka T., Kubuki Y., Kitanaka A., Hidaka M., Nakano N., Utsunomiya A., Sica R.A., Acuna-Villaorduna A., Janakiram M., Shah U., Ramos J.C., Shibata T., Takeuchi K., Takaori-Kondo A., Miyazaki Y., Matsuoka M., Ishitsuka K., Shiraishi Y., Miyano S., Ogawa S., Ye B.H., Shimoda K., Kataoka K.
Blood 139 ( 7 ) 967 - 982 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Blood
Adult T-cell leukemia/lymphoma (ATL) is an aggressive neoplasm immunophenotypically resembling regulatory T cells, associated with human T-cell leukemia virus type-1. Here, we performed whole-genome sequencing (WGS) of 150 ATL cases to reveal the overarching landscape of genetic alterations in ATL. We discovered frequent (33%) loss-of-function alterations preferentially targeting the CIC long isoform, which were overlooked by previous exome-centric studies of various cancer types. Long but not short isoform–specific inactivation of Cic selectively increased CD4+CD25+Foxp3+ T cells in vivo. We also found recurrent (13%) 3′-truncations of REL, which induce transcriptional upregulation and generate gain-of-function proteins. More importantly, REL truncations are also common in diffuse large B-cell lymphoma, especially in germinal center B-cell–like subtype (12%). In the non-coding genome, we identified recurrent mutations in regulatory elements, particularly splice sites, of several driver genes. In addition, we characterized the different mutational processes operative in clustered hypermutation sites within and outside immunoglobulin/T-cell receptor genes and identified the mutational enrichment at the binding sites of host and viral transcription factors, suggesting their activities in ATL. By combining the analyses for coding and noncoding mutations, structural variations, and copy number alterations, we discovered 56 recurrently altered driver genes, including 11 novel ones. Finally, ATL cases were classified into 2 molecular groups with distinct clinical and genetic characteristics based on the driver alteration profile. Our findings not only help to improve diagnostic and therapeutic strategies in ATL, but also provide insights into T-cell biology and have implications for genome-wide cancer driver discovery.
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Kawano N., Saito N., Yoshida S., Kitanaka A., Shide K., Marutsuka K., Ohshima K., Shimoda K.
Tohoku Journal of Experimental Medicine 256 ( 2 ) 119 - 125 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Tohoku Journal of Experimental Medicine
Although splenomegaly is one of the important signs of primary myelofibrosis, the differential diagnosis varies from malignant disorders to benign disorders, including malignant lymphoma and sarcoidosis. The patient was a 67-year-old male who developed anemia and huge splenomegaly. The laboratory findings include human T-cell leukemia virus type 1 (HTLV-1) antibody, elevated soluble interleukin-2 receptor, hypocellular bone marrow, and uptake in the spleen on positron emission tomography/computed tomography scan. Additionally, we performed laparoscopic splenectomy to alleviate the clinical symptoms and to rule out malignant lymphoma. Histological findings revealed extramedullary hematopoiesis, characterized by the presence of erythroid islands and clusters of dysplastic megakaryocytes with increased reticulin fibrosis. Immunohistochemical staining revealed the presence of von Willebrand factor, dysplastic megakaryocytes, myeloperoxidase, myeloid-predominant proliferations, and CD34 immature myeloid cells. Furthermore, regarding the angiogenesis in the spleen, the endothelial cells of the capillaries and those of the sinusoidal vascular system that were reactive for CD34 and CD8, respectively, were also detected. Consequently, the histological findings revealed both extramedullary hematopoiesis and angiogenesis in spleen. Based on the histological findings and the identification of Janus activating kinase 2 (JAK-2) mutation, the patient was diagnosed with primary myelofibrosis. Splenectomy reduces blood transfusion requirements after surgery. The patient was carefully followed-up without further treatments. Thus, primary myelofibrosis is the crucial differential diagnosis of huge splenomegaly.
DOI： 10.1620/tjem.256.119
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Saito N., Yamauchi T., Kawano N., Ono R., Yoshida S., Miyamoto T., Kamimura T., Shultz L.D., Saito Y., Takenaka K., Shimoda K., Harada M., Akashi K., Ishikawa F.
International Journal of Hematology 115 ( 2 ) 198 - 207 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
Introduction: Primary myelofibrosis (PMF) is a clonal stem cell disorder characterized by myeloid dominant hematopoiesis and dysregulated proliferation of fibroblasts in the bone marrow. However, how these aberrant myeloid cells and fibroblasts are produced remains unclear. Aim and methods: In this study, we examined in vivo engraftment kinetics of PMF patient-derived CD34+ cells in immunecompromised NOD/SCID/IL2rgKO (NSG) mice. Engrafted human cells were analyzed with flow cytometry, and proliferation of fibroblastic cells and bone marrow fibrosis were assessed with the histo-pathological examination. Results: Transplantation of PMF patient-derived circulating CD34+ fractions into NSG newborns recapitulates clinical features of human PMF. Engraftment of human CD45+ leukocytes resulted in anemia and myeloid hyperplasia accompanied by bone marrow fibrosis by six months post-transplantation. Fibrotic bone marrow contained CD45-vimentin+ cells of both human and mouse origin, suggesting that circulating malignant CD34+ subsets contribute to myelofibrotic changes in PMF through direct and indirect mechanisms. Conclusion: A patient-derived xenotransplantation (PDX) model of PMF allows in vivo examination of disease onset and propagation originating from immature CD34+ cells and will support the investigation of pathogenesis and development of therapeutic modalities for the disorder.
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Hashimoto Y., Ito T., Gotoh A., Nakamae M., Kimura F., Koike M., Kirito K., Wada H., Usuki K., Tanaka T., Mori T., Wakita S., Saito T.I., Kada A., Saito A.M., Shimoda K., Sugimoto Y., Kurokawa T., Tomita A., Edahiro Y., Akashi K., Matsumura I., Takenaka K., Komatsu N.
International Journal of Hematology 115 ( 2 ) 208 - 221 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
We conducted a large-scale, nationwide retrospective study of Japanese patients who were diagnosed with essential thrombocythemia based on the diagnostic criteria in the World Health Organization classification. We investigated clinical characteristics, survival rates, and the incidence of thrombohemorrhagic events as well as risk factors for these events. A total of 1152 patients were analyzed in the present study. Median age at diagnosis was 65 years, the median platelet count was 832 × 109/L, and the positive mutation rates of JAK2V617F, CALR, and MPL were 62.8, 25.1, and 4.1%, respectively. Compared with European and American patients, Japanese patients were more likely to have cardiovascular risk factors and less likely to have systemic symptoms including palpable splenomegaly. Thrombocytosis was identified as a risk factor for hemorrhagic events and prognosis, but not for thrombotic events. The prognostic factors and risk classifications reported in Europe and the United States were generally applicable to Japanese patients. Regarding transformations, secondary myelofibrosis progressed in a time-dependent manner, but progression to acute leukemia was low in “true” ET patients. Skin cancers were less common and gastrointestinal cancers more common as secondary malignancies in Japanese patients, suggesting ethnic differences.
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Insufficiency of non-canonical PRC1 synergizes with JAK2V617F in the development of myelofibrosis 査読あり
Shinoda D., Nakajima-Takagi Y., Oshima M., Koide S., Aoyama K., Saraya A., Harada H., Rahmutulla B., Kaneda A., Yamaguchi K., Furukawa Y., Koseki H., Shimoda K., Tanaka T., Sashida G., Iwama A.
Leukemia 36 ( 2 ) 452 - 463 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
Insufficiency of polycomb repressive complex 2 (PRC2), which trimethylates histone H3 at lysine 27, is frequently found in primary myelofibrosis and promotes the development of JAK2V617F-induced myelofibrosis in mice by enhancing the production of dysplastic megakaryocytes. Polycomb group ring finger protein 1 (Pcgf1) is a component of PRC1.1, a non-canonical PRC1 that monoubiquitylates H2A at lysine 119 (H2AK119ub1). We herein investigated the impact of PRC1.1 insufficiency on myelofibrosis. The deletion of Pcgf1 in JAK2V617F mice strongly promoted the development of lethal myelofibrosis accompanied by a block in erythroid differentiation. Transcriptome and chromatin immunoprecipitation sequence analyses showed the de-repression of PRC1.1 target genes in Pcgf1-deficient JAK2V617F hematopoietic progenitors and revealed Hoxa cluster genes as direct targets. The deletion of Pcgf1 in JAK2V617F hematopoietic stem and progenitor cells (HSPCs), as well as the overexpression of Hoxa9, restored the attenuated proliferation of JAK2V617F progenitors. The overexpression of Hoxa9 also enhanced JAK2V617F-mediated myelofibrosis. The expression of PRC2 target genes identified in PRC2-insufficient JAK2V617F HSPCs was not largely altered in Pcgf1-deleted JAK2V617F HSPCs. The present results revealed a tumor suppressor function for PRC1.1 in myelofibrosis and suggest that PRC1.1 insufficiency has a different impact from that of PRC2 insufficiency on the pathogenesis of myelofibrosis.
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Kimishima Y., Misaka T., Yokokawa T., Wada K., Ueda K., Sugimoto K., Minakawa K., Nakazato K., Ishida T., Oshima M., Koide S., Shide K., Shimoda K., Iwama A., Ikeda K., Takeishi Y.
Nature Communications 12 ( 1 ) 6177 2021年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Nature Communications
Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice. JAK2V617F-expressing neutrophils specifically accumulate in pulmonary arterial regions, accompanied by increases in neutrophil-derived elastase activity and chemokines in chronic hypoxia-exposed JAK2V617F transgenic (JAK2V617F) mice, as well as recipient mice transplanted with JAK2V617F bone marrow cells. JAK2V617F progressively upregulates Acvrl1 (encoding ALK1) during the differentiation from bone marrow stem/progenitor cells peripherally into mature neutrophils of pulmonary arterial regions. JAK2V617F-mediated STAT3 phosphorylation upregulates ALK1-Smad1/5/8 signaling. ALK1/2 inhibition completely prevents the development of PH in JAK2V617F mice. Finally, our prospective clinical study identified JAK2V617F-positive clonal hematopoiesis is more common in PH patients than in healthy subjects. These findings indicate that clonal hematopoiesis with JAK2V617F causally leads to PH development associated with ALK1 upregulation.
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Komada N., Fujiwara T., Yoshizumi H., Ida H., Shimoda K.
Case Reports in Gastroenterology 15 ( 3 ) 838 - 845 2021年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Case Reports in Gastroenterology
Gaucher disease is a rare genetic disorder caused by the deficiency of acid β-glucosidase to effectively catalyze the degradation of glucosylceramide to glucose and ceramide. We report here the case of a 31-year-old male Japanese patient with Gaucher disease who switched from enzyme replacement therapy (ERT) to substrate reducing therapy (SRT). Liver dysfunction was identified at a routine medical checkup, and the patient was referred to our hospital with "idiopathic liver disease."Clinical laboratory tests indicated thrombocytopenia and splenomegaly, which are characteristic symptoms of Gaucher disease. To definitively diagnose Gaucher disease, a bone marrow biopsy and acid β-glucosidase activity measurement were conducted; the results supported a diagnosis of Gaucher disease. This case emphasizes that it is possible for periodic medical checkups in adults to lead to the diagnosis of rare genetic disorders. The patient underwent ERT treatment with imiglucerase for 5 years; the platelet count rapidly increased and the spleen size rapidly decreased, indicating a good response to the drug. However, the patient increasingly felt the burden of visiting the hospital for 2 h of infusion ERT every 2 weeks. Consequently, it was jointly decided that he should switch from ERT to SRT with an oral drug. This switch was successful with no deterioration of laboratory data. This case report is the first to describe a Japanese Gaucher disease patient treated with eliglustat for >2 years. We showed that SRT is a well-tolerated and effective option for the treatment of Gaucher disease.
DOI： 10.1159/000519005
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Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1. 査読あり
Koya J, Saito Y, Kameda T, Kogure Y, Yuasa M, Nagasaki J, McClure MB, Shingaki S, Tabata M, Tahira Y, Akizuki K, Kamiunten A, Sekine M, Shide K, Kubuki Y, Hidaka T, Kitanaka A, Nakano N, Utsunomiya A, Togashi Y, Ogawa S, Shimoda K, Kataoka K
Blood cancer discovery 2 ( 5 ) 450 - 467 2021年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Association for Cancer Research (AACR)
Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)–infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1–infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell–restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis.
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Fauzi Y.R., Nakahata S., Chilmi S., Ichikawa T., Nueangphuet P., Yamaguchi R., Nakamura T., Shimoda K., Morishita K.
PLoS ONE 16 ( 8 August ) e0256320 2021年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：PLoS ONE
Adult T-cell leukemia/lymphoma (ATLL) originates from human T-cell leukemia virus type 1 (HTLV-1) infection due to the activation of the nuclear factor-κB (NF-κB) signaling pathway to maintain proliferation and survival. An important mechanism of the activated NF-κB signaling pathway in ATLL is the activation of the macroautophagy (herafter referred to as autophagy in the remainder of this manuscript)-lysosomal degradation of p47 (NSFL1C), a negative regulator of the NF-κB pathway. Therefore, we considered the use of chloroquine (CQ) or hydroxychloroquine (HCQ) (CQ/HCQ) as an autophagy inhibitor to treat ATLL; these drugs were originally approved by the FDA as antimalarial drugs and have recently been used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE). In this paper, we determined the therapeutic efficacy of CQ/HCQ, as NF-κB inhibitors, in ATLL mediated by blockade of p47 degradation. Administration of CQ/HCQ to ATLL cell lines and primary ATLL cells induced cell growth inhibition in a dose-dependent manner, and the majority of cells underwent apoptosis after CQ administration. As to the molecular mechanism, autophagy was inhibited in CQ-treated ATLL cells, and activation of the NF-κB pathway was suppressed with the restoration of the p47 level. When the antitumor effect of CQ/ HCQ was examined using immunodeficient mice transplanted with ATLL cell lines, CQ/ HCQ significantly suppressed tumor growth and improved the survival rate in the ATLL xenograft mouse model. Importantly, HCQ selectively induced ATLL cell death in the ATLL xenograft mouse model at the dose used to treat SLE. Taken together, our results suggest that the inhibition of autophagy by CQ/HCQ may become a novel and effective strategy for the treatment of ATLL.
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Nakamura K, Kusumoto K, Ozono Y, Kuroki K, Matsuura Y, Mukuda T, Ochiai T, Tsuchimochi M, Iwakiri H, Hasuike S, Shimoda K, Nagata K
Anticancer research 41 ( 8 ) 4127 - 4131 2021年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Anticancer Research
Background/Aim: Direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection deliver higher cure rates and lower frequencies of adverse events than existing therapies, though DAA treatment costs $45,000-64,000 in Japan. The prognosis of patients who require new long-term care insurance (LTCI) certification is inferior to that of patients who do not. Here, we clarify the factors associated with new LTCI certification in elderly patients with HCV infection who undergo DAA therapy. Patients and Methods: We retrospectively surveyed 53 patients aged ≥70 years who were treated with DAAs, and evaluated the factors associated with new LTCI certification. Results: Of 53 patients, 10 required new LTCI certification. Age ≥85 years and a modified Japanese Cardiovascular Health Study index ≥2 were independently associated with new LTCI certification. Conclusion: In elderly HCV patients, poor frailty status strongly predicted new LTCI certification after DAA therapy.
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Takeshima H, Yoshikawa N, Akizuki K, Hidaka T, Shimoda K, Ikeda R
Journal of clinical pharmacy and therapeutics 47 ( 2 ) 260 - 262 2021年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Pharmacy and Therapeutics
What is known and objective: Cyclosporine A (CyA) causes intrahepatic biliary stasis via inhibition of bile acid excretion through the bile salt export pump. We report a case of a patient in whom ursodeoxycholic acid (UDCA) markedly promoted the absorption of microemulsion-formulated CyA. Case summary: The patient was a 22-year-old Japanese man diagnosed with stage 3 aplastic anaemia. He was treated with CyA, and 2 h post-dose (C2) was increased by UDCA. What is new and conclusion: A remarkable interaction was observed between CyA and UDCA. This is a valuable finding for improving the treatment strategies for haematological disorders.
DOI： 10.1111/jcpt.13496
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Yoshikawa N., Takeshima H., Sekine M., Akizuki K., Hidaka T., Shimoda K., Ikeda R.
Pharmaceuticals 14 ( 4 ) 2021年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pharmaceuticals
A polymorphism in the gene encoding the metabolic enzyme cytochrome P450 family 3 subfamily A member 5 (CYP3A5) is a particularly influential factor in the use of tacrolimus in Japanese patients. Those who are homozygotic for the *3 mutation lack CYP3A5 activity, which results in substantial individual differences in tacrolimus metabolism. The aim of this study was to analyze the relationship between individual differences in tacrolimus blood concentration changes and CYP3A5 polymorphisms in allogeneic hematopoietic stem cell transplantation recipients during the period of increasing blood concentration of the drug following treatment onset. This was a prospective observational cohort study, involving 20 patients administered tacrolimus by continuous infusion. The subjects were divided into the *1/*3 and *3/*3 groups based on CYP3A5 polymorphism analysis. The tacrolimus blood concentration/dose (C/D) ratio increased from day 1 and was largely stable on day 5, and a significant difference was observed between the *1/*3 and *3/*3 groups in the time course of the C/D ratio during this period (p < 0.05). This study reveals the effects om on continuous changes in tacrolimus blood concentration.
DOI： 10.3390/ph14040353
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Sekine M., Kameda T., Shide K., Maeda K., Toyama T., Kawano N., Takeuchi M., Kawano H., Sato S., Ishizaki J., Kukita T., Kamiunten A., Akizuki K., Tahira Y., Shimoda H., Hidaka T., Yamashita K., Matsuoka H., Kitanaka A., Kubuki Y., Shimoda K.
European Journal of Haematology 106 ( 3 ) 398 - 407 2021年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：European Journal of Haematology
Objective and Method: Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell lymphoma with poor prognosis. We retrospectively reviewed the medical records of 312 patients with aggressive ATL and analyzed the effect of chemotherapy dose intensity on prognosis in clinical practice. Result: As first-line therapy, 62 patients underwent best supportive care (BSC) or single-agent chemotherapy, and 235 underwent intensive chemotherapy. The median survival time (MST) was 0.58 years in the 312 total patients, and 0.13 years and 0.75 years in the BSC/single-agent chemotherapy group and intensive chemotherapy group, respectively. The median average relative dose intensity (ARDI) of patients who received intensive chemotherapy was 60%. We divided patients into 3 groups according to ARDI. Those in the top tertile of ARDI (ARDI ≥ 75%, n = 82) had better overall survival compared with those in the intermediate tertile (45% ≤ ARDI < 75%, n = 79) (P <.0001), with MSTs of 4.69 and 0.75 years, respectively. The occurrence of organ dysfunction and infectious complications was comparable between the two ARDI groups. Conclusion: Higher ARDI improves prognosis in patients with aggressive ATL in clinical practice.
DOI： 10.1111/ejh.13565
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Kawano N., Kawano S., Yoshida S., Kuriyama T., Tochigi T., Nakaike T., Shimokawa T., Yamashita K., Ochiai H., Shimoda K., Mashiba K., Kikuchi I.
Journal of Echocardiography 19 ( 1 ) 45 - 52 2021年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Echocardiography
Background: Although anthracycline-related cardiomyopathy is a life-threatening complication during intensive treatment for hematological malignancies, clinical features and outcomes of this type of cardiomyopathy have been unclear because of limited reports in the literature. Methods: We analyzed three cases of anthracycline-related cardiomyopathy among 996 patients with either acute myelogenous leukemia (285), acute lymphoblastic leukemia (37), or malignant lymphoma (674) at our hospital during the period from 2006 to 2016. Results: All patients showed accumulation of anthracycline within a proper range (< 500 mg/sqm). Two patients (Hodgkin lymphoma and acute lymphoblastic leukemia) showed acute heart failure (AHF) with ejection fraction (EF) of 30 and 40% after 4.5 and 5 years after diagnosis, respectively. For AHF, diuretics and carperitide were administered to control in–out balance. The remaining patient (follicular lymphoma) showed ventricular fibrillation (VF)/ventricular tachycardia (VT) with EF of 40% at 5 years after diagnosis. In this patient, immediate cardioversion made VF/VT to normal sinus rhythm, and then, amiodarone was given. Furthermore, implantable cardioverter defibrillator was set up for VF/VT. In all patients, β blocker and/or angiotensin-converting enzyme inhibitor (ACE-I) were administrated to prevent recurrence of anthracycline-related cardiomyopathy. Consequently, two of three patients showed mild improvement of cardiac function. Conclusion: Our study indicates that late-onset (4 to 5 years) anthracycline-related cardiomyopathy can develop, though range of anthracycline accumulation is in proper range. Thus, a cautious follow-up by ECG and UCG is required. Furthermore, the early treatment after the onset of anthracycline-related cardiomyopathy should be also needed to improve the poor outcome.
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Ozono Y., Shide K., Kameda T., Kamiunten A., Tahira Y., Sekine M., Akizuki K., Nakamura K., Iwakiri H., Sueta M., Hidaka T., Kubuki Y., Yamamoto S., Hasuike S., Sawaguchi A., Nagata K., Shimoda K.
Leukemia 35 ( 2 ) 454 - 467 2021年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-β1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. In this study, we showed that the vast majority of collagen- and fibronectin-producing cells in the BM and spleens of Jak2V617F-induced myelofibrosis (MF) mice were fibrocytes derived from neoplastic hematopoietic cells. Neoplastic monocyte depletion eliminated collagen- and fibronectin-producing fibrocytes in BM and spleen, and ameliorated most characteristic MF features in Jak2V617F transgenic mice, including BM fibrosis, anemia, and splenomegaly, while had little effect on the elevated numbers of megakaryocytes and stem cells in BM, and leukothrombocytosis in peripheral blood. TGF-β1, which was produced by hematopoietic cells including fibrocytes, promoted the differentiation of neoplastic monocytes to fibrocytes, and elevated plasma TGF-β1 levels were normalized by monocyte depletion. Collectively, our data suggest that neoplastic fibrocytes are the major contributor to BM fibrosis in PMF, and TGF-β1 is required for their differentiation.
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Akizuki K., Matsuoka H., Toyama T., Kamiunten A., Sekine M., Shide K., Kameda T., Kawano N., Maeda K., Takeuchi M., Kawano H., Sato S., Ishizaki J., Tahira Y., Shimoda H., Hidaka T., Yamashita K., Kubuki Y., Shimoda K.
Journal of Clinical Medicine 10 ( 1 ) 1 - 9 2021年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Medicine
The prognosis of multiple myeloma (MM) has improved with the introduction of novel agents. These data are largely derived from clinical trials and might not reflect real-world patient outcomes accurately. We surveyed real-world data from 284 patients newly diagnosed with MM between 2010 and 2018 in Miyazaki Prefecture. The median follow-up period was 32.8 months. The median age at diagnosis was 71 years, with 68% of patients aged >65 years. The International Staging System (ISS) stage at diagnosis was I in 18.4% of patients, II in 34.1%, and III in 47.5%. Bortezomib-containing regimens were preferred as initial treatment; they were used in 147 patients (51.8%). In total, 80% of patients were treated with one or more novel agents (thalidomide, lenalidomide, or bortezomib). Among 228 patients who were treated with novel agents as an initial treatment, the overall response rate (partial response (PR) or better) to initial treatment was 78.4%, and the median time to next treatment (TTNT) was 11.6 months. In the multivariate analysis, PR or better responses to initial treatment were independently favorable prognostic factors for TTNT. The median survival time after initial therapy for patients with novel agents was 56.4 months and 3-year overall survival (OS) was 70.4%. In multivariate analysis, ISS stage I/II disease and PR or better response to initial treatment, and autologous stem cell transplantation (ASCT) were identified as independent prognostic factors for overall survival (OS).
DOI： 10.3390/jcm10010105
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Miike T., Kawakami H., Kameda T., Yamamoto S., Tahara Y., Hidaka T., Kubuki Y., Yorita K., Akiyama Y., Arimura Y., Kubota Y., Kataoka H., Shimoda K.
BMC Gastroenterology 20 ( 1 ) 298 2020年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Gastroenterology
Background: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1. The clinical course of ATLL is very heterogeneous, and many organs, including the gastrointestinal (GI) tract, can be involved. However, there are few detailed reports on ATLL infiltration in the GI tract. We investigated the clinical characteristics of ATLL infiltration in the GI tract. Methods: This retrospective observational single-center study included 40 consecutive ATLL patients who underwent GI endoscopy. The patients' demographic and clinical characteristics and endoscopic findings were analyzed retrospectively. Patients with ATLL who were diagnosed by histological examination were divided into two groups based on GI tract infiltration. Results: Multivariate analysis revealed that the absence of skin lesions was significantly associated with GI infiltration (P < 0.05). Furthermore, the infiltration group tended to have similar macroscopic lesions in the upper and lower GI tracts, such as diffuse type, tumor-forming type, and giant-fold type. Conclusions: GI endoscopy may be considered for ATLL patients without skin lesions.
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Uterine relapse of Philadelphia chromosome-negative acute lymphoblastic leukemia. 査読あり
Kawano N, Maeda T, Kawano S, Naghiro Y, Takami A, Tochigi T, Nakaike T, Yamashita K, Kodama T, Marutsuka K, Sugimoto Y, Imamura T, Mori Y, Ochiai H, Hidaka T, Shimoda K, Mashiba K, Kikuchi I
Journal of clinical and experimental hematopathology : JCEH 60 ( 3 ) 103 - 107 2020年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本リンパ網内系学会
The relapse of acute lymphoblastic leukemia (ALL) usually involves the bone marrow, with the central nervous system being the most frequent extramedullary site. The relapse of ALL in the female genital organs, particularly the uterus, is markedly rare. We report such a patient who developed relapse in the bone marrow and uterus. The uterine lesion, which presented as abnormal uterine bleeding, consisted of a mass on MRI and proliferation of ALL cells on histology. MRI revealed a heterogeneous high-intensity mass (T2-WI/D-WI) with a diameter of 6.8 cm, a notable decrease in the apparent diffusion coefficient (ADC), and mild enhancement by contrast enhancement study. Histological findings of the uterine cervix demonstrated the infiltration of ALL. The patient achieved remission by allogeneic haplo-identical hematopoietic stem-cell transplantation, but died of complications of the transplantation. This case suggested that attention should be paid to the uterus as a site of extramedullary relapse. In addition, abnormal uterine bleeding, which is a common sign of hormonal imbalance and hormone replacement therapy after chemotherapy, may be an initial sign of extramedullary recurrence. To confirm uterine relapse as an intractable disease, the accumulation of more cases is required.
DOI： 10.3960/jslrt.20016
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Fagnan A., Bagger F.O., Piqué-Borràs M.R., Ignacimouttou C., Caulier A., Lopez C.K., Robert E., Uzan B., Gelsi-Boyer V., Aid Z., Thirant C., Moll U., Tauchmann S., Kurtovic-Kozaric A., Maciejewski J., Dierks C., Spinelli O., Salmoiraghi S., Pabst T., Shimoda K., Deleuze V., Lapillonne H., Sweeney C., de Mas V., Leite B., Kadri Z., Malinge S., de Botton S., Micol J.B., Kile B., Carmichael C.L., Iacobucci I., Mullighan C.G., Carroll M., Valent P., Bernard O.A., Delabesse E., Vyas P., Birnbaum D., Anguita E., Garçon L., Soler E., Schwaller J., Mercher T.
Blood 136 ( 6 ) 698 - 714 2020年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Blood
Acute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes. To better define the underlying molecular mechanisms driving the erythroid phenotype, we studied a series of 33 AEL samples representing 3 genetic AEL subgroups including TP53-mutated, epigenetic regulator-mutated (eg, DNMT3A, TET2, or IDH2), and undefined cases with low mutational burden. We established an erythroid vs myeloid transcriptome-based space in which, independently of the molecular subgroup, the majority of the AEL samples exhibited a unique mapping different from both non-M6 AML and myelodysplastic syndrome samples. Notably, >25% of AEL patients, including in the genetically undefined subgroup, showed aberrant expression of key transcriptional regulators, including SKI, ERG, and ETO2. Ectopic expression of these factors in murine erythroid progenitors blocked in vitro erythroid differentiation and led to immortalization associated with decreased chromatin accessibility at GATA1-binding sites and functional interference with GATA1 activity. In vivo models showed development of lethal erythroid, mixed erythroid/myeloid, or other malignancies depending on the cell population in which AEL-associated alterations were expressed. Collectively, our data indicate that AEL is a molecularly heterogeneous disease with an erythroid identity that results in part from the aberrant activity of key erythroid transcription factors in hematopoietic stem or progenitor cells.
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Shide K., Kameda T., Kamiunten A., Ozono Y., Tahira Y., Yokomizo-Nakano T., Kubota S., Ono M., Ikeda K., Sekine M., Akizuki K., Nakamura K., Hidaka T., Kubuki Y., Iwakiri H., Hasuike S., Nagata K., Sashida G., Shimoda K.
Blood 136 ( 1 ) 106 - 118 2020年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Blood
Mutations in JAK2, myeloproliferative leukemia virus (MPL), or calreticulin (CALR) occur in hematopoietic stem cells (HSCs) and are detected in more than 80% of patients with myeloproliferative neoplasms (MPNs). They are thought to play a driver role in MPN pathogenesis via autosomal activation of the JAK-STAT signaling cascade. Mutant CALR binds to MPL, activates downstream MPL signaling cascades, and induces essential thrombocythemia in mice. However, embryonic lethality of Calr-deficient mice precludes determination of a role for CALR in hematopoiesis. To clarify the role of CALR in normal hematopoiesis and MPN pathogenesis, we generated hematopoietic cell-specific Calr-deficient mice. CALR deficiency had little effect on the leukocyte count, hemoglobin levels, or platelet count in peripheral blood. However, Calr-deficient mice showed some hematopoietic properties of MPN, including decreased erythropoiesis and increased myeloid progenitor cells in the bone marrow and extramedullary hematopoiesis in the spleen. Transplantation experiments revealed that Calr haploinsufficiency promoted the self-renewal capacity of HSCs. We generated CALRdel52 mutant transgenic mice with Calr haploinsufficiency as a model that mimics human MPN patients and found that Calr haploinsufficiency restored the self-renewal capacity of HSCs damaged by CALR mutations. Only recipient mice transplanted with Lineage−Sca1+c-kit+ cells harboring both CALR mutation and Calr haploinsufficiency developed MPN in competitive conditions, showing that CALR haploinsufficiency was necessary for the onset of CALR-mutated MPNs. Key Points: • Calr deficiency induces reduction of erythropoiesis in the bone marrow and extramedullary hematopoiesis in the spleen. • CALR haploinsufficiency restores the self-renewal capacity of HSCs damaged by CALR del52 and is required for the development of MPN.
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Hirashima K., Muromoto R., Minoguchi H., Matsumoto T., Kitai Y., Kashiwakura J.i., Shimoda K., Oritani K., Matsuda T.
Cytokine 130 25 - 34 2020年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cytokine
© 2020 Elsevier Ltd Macrophages are highly plastic in their pro-inflammatory/anti-inflammatory roles. Type I and II interferons (IFNs) are known to modulate macrophage activation. Tyrosine kinase 2 (Tyk2) has an intimate relationship with type I and II IFN signaling. Animal studies have shown that Tyk2 knock-out (KO) in mice is associated with reduced inflammatory responses in various mouse models of diseases. To investigate the role of Tyk2 in inflammation in more detail, we intraperitoneally injected heat-killed Propionibacterium acnes (P. acnes) to Tyk2 KO mice. P. acnes–induced acute peritoneal inflammation, assessed by neutrophil infiltration, was reduced in Tyk2 KO mice. The reduction was accompanied with diminished productions of inflammatory cytokines and an enhanced production of anti-inflammatory IL-10. Unexpectedly, pre-treatment of wild-type mice with the neutralizing antibodies for IFNs did not affect P. acnes-induced neutrophil infiltration. A neutralizing antibody for the IL-10 receptor in Tyk2 KO mice restored P. acnes-induced peritoneal inflammation. Enhanced production of IL-10 from Tyk2 KO peritoneal cells was suppressed by either the cyclooxygenase inhibitor diclofenac or protein kinase A inhibitor H-89. The level of prostaglandin E2 (PGE2) in the steady-state peritoneal cavity in Tyk2 KO mice was higher than that in wild-type mice. Tyk2 KO macrophages showed an enhanced CREB phosphorylation induced by P. acnes plus PGE2. Taken together, these results showed that Tyk2 deficiency potentiates the PGE2-protein kinase A-IL-10 pathway in macrophages, and thereby contributes to potentiation of the immunosuppressive phenotype.
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Single Rectal Neuroendocrine Tumor Associated with Multiple Endocrine Cell Micronests 査読あり
Suzuki S., Kawakami H., Miike T., Yamamoto S., Abe H., Shimoda K., Ashizuka S., Inatsu H., Kubota Y., Ban T., Yorita K., Kataoka H.
Internal Medicine 59 ( 5 ) 619 - 623 2020年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
© 2020 Japanese Society of Internal Medicine. All rights reserved. Although a few reports of neuroendocrine tumor (NET) in the stomach or appendix with surrounding micronests have been published, cases of rectal NET are rare. We herein report a unique case of a patient with single rectal NET treated endoscopically. A pathological examination revealed multiple endocrine cell micronests (ECMs) in the submucosal layer around the main NET lesion. Neither lymph node metastasis nor distant metastasis in computed tomography was observed six years after the treatment. Because case reports of multiple ECM are very rare, the significance of malignancy is unclear. It therefore appears to be necessary to accumulate similar cases.
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Clinical significance of soluble CADM1 as a novel marker for adult T-cell leukemia/lymphoma. 査読あり
Nakahata S, Syahrul C, Nakatake A, Sakamoto K, Yoshihama M, Nishikata I, Ukai Y, Matsuura T, Kameda T, Shide K, Kubuki Y, Hidaka T, Kitanaka A, Ito A, Takemoto S, Nakano N, Saito M, Iwanaga M, Sagara Y, Mochida K, Amano M, Maeda K, Sueoka E, Okayama A, Utsunomiya A, Shimoda K, Watanabe T, Morishita K
Haematologica 106 ( 2 ) 532 - 542 2020年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Haematologica
Adult T-cell leukemia/leukemia (ATLL) is an aggressive peripheral T-cell malignancy, caused by infection with the human T-cell leukemia virus type 1 (HTLV-1). We recently showed that the cell adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, is specifically and consistently overexpressed in ATLL cells, and functions as a novel cell surface marker. In this study, we first show that a soluble form of CADM1 (sCADM1) is secreted from ATLL cells by mainly alternative splicing. After developing the Alpha linked immunosorbent assay (AlphaLISA) for sCADM1, we show that plasma sCADM1 concentrations gradually increased during disease progression from indolent to aggressive ATLL. Although other known biomarkers of tumor burden such as soluble interleukin-2 receptor α (sIL-2Rα) also increased with sCADM1 during ATLL progression, multivariate statistical analysis of biomarkers revealed that only plasma sCADM1 was selected as a specific biomarker for aggressive ATLL, suggesting that plasma sCADM1 may be a potential risk factor for aggressive ATLL. In addition, plasma sCADM1 is a useful marker for monitoring response to chemotherapy as well as for predicting relapse of ATLL. Furthermore, the change in sCADM1 concentration between indolent and aggressive type ATLL was more prominent than the change in the percentage of CD4+CADM1+ ATLL cells. As plasma sCADM1 values fell within normal ranges in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with higher levels of serum sIL-2Rα, the measurement of sCADM1 may become a useful tool to discriminate between ATLL and other inflammatory diseases, including HAM/TSP.
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Ichikawa T., Shanab O., Nakahata S., Shimosaki S., Manachai N., Ono M., Iha H., Shimoda K., Morishita K.
Biochimica et Biophysica Acta - Molecular Cell Research 1867 ( 2 ) 118615 2020年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochimica et Biophysica Acta - Molecular Cell Research
N-myc downstream-regulated gene 2 (NDRG2) as a tumor suppressor is frequently downregulated in human T-lymphotropic retrovirus (HTLV-1)-infected adult T-cell leukemia (ATL) and variety of cancers, and negatively regulates PI3K signaling pathways through dephosphorylation of PTEN with protein phosphatase 2A (PP2A). We recently identified that protein arginine methyltransferase 5 (PRMT5) is one of novel NDRG2 binding proteins and the knockdown of PRMT5 induces cell apoptosis with degradation of several signaling molecules. To investigate how the apoptosis is induced by the knockdown PRMT5 expression, heat shock protein 90 alpha (HSP90A) was identified as a binding protein for NDRG2 or PRMT5 by immunoprecipitation-mass analysis. NDRG2/PP2A complex inhibited arginine methyltransferase activity of PRMT5 through dephosphorylation at Serine 335 (S335); however, in NDRG2low ATL-related cells, highly phosphorylated PRMT5 at S335 was mainly localized in cytoplasm with binding to HSP90A, resulting in enhancing arginine-methylation at the middle domain (R345 and R386). Since knockdown of PRMT5 expression or forced expression of HSP90A with alanine replacement of R345 or R386 induced apoptosis with the degradation of client proteins in NDRG2low ATL-related and other cancer cells, we here identified that the novel arginine methylations of HSP90A are essential for maintenance of its function in NDRG2low ATL and other cancer cells.
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Akizuki K., Sekine M., Kogure Y., Kameda T., Shide K., Koya J., Kamiunten A., Kubuki Y., Tahira Y., Hidaka T., Kiwaki T., Tanaka H., Sato Y., Kataoka H., Kataoka K., Shimoda K.
BMC Cancer 20 ( 1 ) 5 2020年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Cancer
© 2019 The Author(s). Background: The occurrence of a mediastinal germ cell tumor (GCT) and hematological malignancy in the same patient is very rare. Due to its rarity, there have been only two reports of the concurrent cases undergoing detailed genetic analysis with whole-exome sequencing (WES), and the possible clonal relationship between the both tumors remained not fully elucidated. Methods: We performed whole-exome sequencing analysis of mediastinal GCT and acute myeloid leukemia (AML) samples obtained from one young Japanese male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them. Results: Sixteen somatic mutations were detected in the mediastinal GCT sample and 18 somatic mutations in the AML sample. Mutations in nine genes, including TP53 and PTEN both known as tumor suppressor genes, were shared in both tumors. Conclusions: All in our case and in the previous two cases with concurrent mediastinal GCT and AML undergoing with whole-exome sequencing analysis, TP53 and PTEN mutations were commonly shared in both tumors. These data not only suggest that these tumors share a common founding clone, but also indicate that associated mediastinal GCT and AML harboring TP53 and PTEN mutations represent a unique biological entity.
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Ogasawara T., Kawauchi K., Ono T., Marshall S., Shide K., Shimoda K., Mori N., Sakura H.
Leukemia Research Reports 13 100194 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia Research Reports
© 2019 The Author(s) Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm (MPN) with a transformation to acute myeloid leukemia in <5% of patients. A 79-year-old man with JAK2V617F-positive ET exhibited leukocytosis with an increase in monoblastic cells, leading to a diagnosis of acute monoblastic and monocytic leukemia. Leukemic cells carried a TET2 mutation but not JAK2V617F mutation. We concluded that the TET2 mutation occurred in MPN-initiating cells and overcame JAK2-mutated cells. The absence of a JAK2 mutation in the leukemic cells in this case suggests the leukemia emerged from a JAK2-negative MPN cell clone carrying the TET2 mutation.
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Kai K., Hamada T., Hiyoshi M., Imamura N., Yano K., Nagano M., Kai M., Hidaka T., Shimoda K., Haruyama Y., Kataoka H., Nanashima A.
International Journal of Surgery Case Reports 76 19 - 24 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Surgery Case Reports
Introduction: Gallbladder involvement in lymphoma is extremely rare, and only 68 cases have been reported in the English literature so far. We experienced a case of diffuse large B-cell lymphoma (DLBCL) of the gallbladder arising 8 years after DLBCL of the right testis. Presentation of case: A 68-year-old man underwent orchiectomy for malignant lymphoma of the right testis pathologically diagnosed as DLBCL 8 years ago. Systemic surveillance incidentally revealed a gallbladder tumour, and elective resection of the gallbladder bed of the liver was performed under a preoperative diagnosis of gallbladder cancer. The histopathological examination revealed DLBCL. At re-evaluation 3 months after surgery, he was diagnosed as having DLBCL involving the stomach. There had been no recurrence for 39 months after chemotherapy and radiation, but he suffered from a poor general condition due to protein-losing enteropathy and died of infection. Discussion: We compiled and analysed reported cases of malignant lymphomas involving the gallbladder in terms of background, symptoms, imaging findings, and prognosis. Compared to MALT lymphoma, DLBCL was significantly more involved in other organs simultaneously or heterochronously (p = 0.004). Conclusion: Gallbladder lymphoma should be added to the differential diagnosis of gallbladder tumours, especially when clinical findings are not consistent with the typical course of gallbladder carcinoma and cholecystitis.
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Clinical features and treatment outcomes of opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia-lymphoma (ATL) at a single institution from 2006 to 2016
NoriakiKawano,YuriNagahiro,_ShuroYoshida,_YoshihiroTahara,_DaisukeHimeji,_TakuroKuriyama,_TaroTochigi,_TakashiNakaike,_TomonoriShimokawa,_KiyoshiYamashita,_HidenobuOchiai,_KouskeMarutsuka,_KoichiMashiba,_KazuyaShimoda,_TakanoriTeshima,_Ikuo Kikuchi
Journal of clinical and experimental hematopathology 59 ( 4 ) 156 - 167 2019年12月
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Essential thrombocytosis attributed to JAK2-T875N germline mutation.
Makoto Yoshimitsu, Miho Hachiman, Yuichiro Uchida, Naosuke Arima, Akihiko Arai, Yuhei Kamada, Kotaro Shide, Masafumi Ito, Kazuya Shimoda, Kenji Ishitsuka
International journal of hematology. 110 ( 5 ) 584 - 590 2019年11月
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The regulation of NDRG2 expression during ATLL development after HTLV-1 infection. 査読あり
Ichikawa T., Nakahata S., Fujii M., Iha H., Shimoda K., Morishita K.
Biochimica et Biophysica Acta - Molecular Basis of Disease 1865 ( 10 ) 2633 - 2646 2019年10月
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Monocyte-derived fibrocytes elimination had little contribution on liver fibrosis 査読あり
Ozono Y., Shide K., Toyoshima F., Takaishi Y., Tsuchimochi M., Kamiunten A., Kameda T., Nakamura K., Miike T., Kusumoto K., Iwakiri H., Hasuike S., Nagata K., Sawaguchi A., Shimoda K.
Hepatobiliary and Pancreatic Diseases International 18 ( 4 ) 348 - 353 2019年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hepatobiliary and Pancreatic Diseases International
© 2019 First Affiliated Hospital, Zhejiang University School of Medicine in China Background: Monocyte-derived fibrocytes play an important role in the progression of fibrosis in the skin, lungs, heart and kidney. However, the contribution of fibrocytes to liver fibrosis is unclear. The aim of this study was to investigate whether fibrocytes contributed to fibrosis progression in the livers of carbon tetrachloride (CCl4)-treated mice. Methods: C57BL/6J mice were divided into 4 groups: normal control group, CCl4-treated group, CCl4 + control liposome-treated group, and CCl4 + clodronate liposome-treated group. For the elimination of systemic monocyte and monocyte-derived fibrocyte, one group was treated with clodronate liposome, and another group with control liposome as a control. After 4 weeks of treatment, hepatic mononuclear cells were subjected to immunofluorescent (IF) staining and fluorescence-activated cell sorter (FACS) analysis to detect fibrocytes. Measurement of collagen-positive Sirius red stained area and collagen-I mRNA expression in the liver were performed to evaluate the degree of liver fibrosis quantitatively. Results: In the liver of the CCl4-treated and CCl4 + control liposome-treated groups, the number of fibrocytes, the area positive for Sirius red staining and collagen-I mRNA expression significantly increased compared with those in the normal control group. In the liver of the CCl4 + clodronate liposome-treated group, few fibrocytes was observed as in the normal control group, but Sirius red staining positive area and collagen-I mRNA expression were increased and equivalent to the CCl4-treated and CCl4 + control liposome-treated groups. Conclusion: Monocyte-derived fibrocytes play a minimal role in CCl4-induced liver fibrosis. Cells other than fibrocytes such as hepatic stellate cells play a central role in liver fibrosis.
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A Case of Acute Liver Failure due to Severe Hepatic Metastasis of Small-cell Lung Cancer Producing Adrenocorticotropic Hormone Complicating Ectopic Cushing Syndrome. 査読あり
Sonoko Kamijo, Satoru Hasuike, Kenichi Nakamura, Yuuka Takaishi, Yuri Yamada, Yoshinori Ozono, Mai Tsuchimochi, Mitsue Sueta, Kazunori Kusumoto, Hisayoshi Iwakiri, Mayumi Akaki, Hiroyuki Tanaka, Hiroaki Kataoka, Kazuya Shimoda, Kenji Nagata:
International journal of hematology. 58 ( 20 ) 2977 - 2982 2019年6月
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Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis. 査読あり
Kotaro Shide, Takuro Kameda, Ayako Kamiunten, Asami Oji, Yoshinori Ozono, Masaaki Sekine, Arata Honda, Akira Kitanaka, Keiichi Akizuki, Yuki Tahira, Kenichi Nakamura, Tomonori Hidaka, Yoko Kubuki, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Mitsue Sueta, Satoru Hasuike, Shojiro Yamamoto, Kenji Nagata, Masahito Ikawa & Kazuya Shimoda
Blood cancer journal 9 ( 4 ) 42 2019年5月
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Molecular heterogeneity in peripheral T-cell lymphoma, not otherwise specified revealed by comprehensive genetic profiling.
Yosaku Watatani, Yasuharu Sato, Hiroaki Miyoshi, Kana Sakamoto, Kenji Nishida, Yuka Gion, Yasunobu Nagata, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Lanying Zhao, Yotaro Ochi, Yasuhide Takeuchi, June Takeda, Hiroo Ueno, Yasunori Kogure, Yusuke Shiozawa, Nobuyuki Kakiuchi, Tetsuichi Yoshizato, Masahiro M. Nakagawa, Yasuhito Nanya, Kenichi Yoshida, Hideki Makishima, Masashi Sanada, Mamiko Sakata-Yanagimoto, Shigeru Chiba, Ryota Matsuoka, Masayuki Noguchi, Nobuhiro Hiramoto, Takayuki Ishikawa, Junichi Kitagawa, Nobuhiko Nakamura, Hisashi Tsurumi, Tatsuhiko Miyazaki, Yusuke Kito, Satoru Miyano, Kazuya Shimoda, Kengo Takeuchi, Koichi Ohshima, Tadashi Yoshino, Seishi Ogawa, Keisuke Kataoka:
Leukemia 33 ( 12 ) 2867 - 2883 2019年5月
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IκB-ζ Expression Requires Both TYK2/STAT3 Activity and IL-17–Regulated mRNA Stabilization.
Ryuta Muromoto, Keisuke Tawa, Yui Ohgakiuchi, Ami Sato, Yuka Saino, Koki Hirashima, Hiroya Minoguchi, Yuichi Kitai, Jun-ichi Kashiwakura, Kazuya Shimoda, Kenji Oritani and Tadashi Matsuda:
ImmunoHorizons. 3 ( 5 ) 172 - 185 2019年5月
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Vitamin D receptor-mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis. 査読あり
Kanako Wakahashi, Kentaro Minagawa, Yuko Kawano, Hiroki Kawano, Tomohide Suzuki, Shinichi Ishii, Akiko Sada, Noboru Asada, Mari Sato, Shigeaki Kato, Kotaro Shide, Kazuya Shimoda, Toshimitsu Matsui and Yoshio Katayama
Blood 133 ( 15 ) 1619 - 1629 2019年4月
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大腸憩室多発領域に炎症が限局し、憩室性大腸炎との鑑別を要したアメーバ性大腸炎の1例
山本章二朗、小村杏奈、前村幸輔、後藤敏之、三池忠、田原良博、丸塚浩助、菊池郁夫、下田和哉
日本消化器内視鏡学会雑誌 61 ( 4 ) 381 - 386 2019年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-κB. 査読あり
Sarkar B., Nishikata I., Nakahata S., Ichikawa T., Shiraga T., Saha H., Fujii M., Tanaka Y., Shimoda K., Morishita K.
Scientific reports 9 ( 1 ) 3491 2019年3月
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Efficacy and safety of sofosbuvir and ledipasvir in japanese patients aged 75 years or over with hepatitis C genotype 1. 査読あり
Ozono Y, Nagata K, Hasuike S, Iwakiri H, Nakamura K, Tsuchimochi M, Yamada Y, Takaishi Y, Sueta M, Miike T, Tahara Y, Yamamoto S, Shide K, Hidaka T, Kubuki Y, Kusumoto K, Ochiai T, Kato J, Komada N, Hirono S, Kuroki K, Shigehira M, Shimoda K
World Journal of Hepatology. 9 ( 36 ) 1340 - 1345 2018年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Kamiunten A., Shide K., Kameda T., Ito M., Sekine M., Kubuki Y., Hidaka T., Akizuki K., Tahira Y., Toyama T., Kawano N., Marutsuka K., Maeda K., Takeuchi M., Kawano H., Sato S., Ishizaki J., Shimoda H., Yamashita K., Matsuoka H., Shimoda K.
International Journal of Hematology 108 ( 4 ) 411 - 415 2018年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
© 2018, The Japanese Society of Hematology. A new entity, namely early/prefibrotic primary myelofibrosis (PMF), was introduced as a subtype of PMF in the 2016 revised World Health Organization (WHO) criteria for myeloproliferative neoplasms (MPN). It was diagnosed based on histopathological features of bone marrow (BM) biopsy specimens together with clinical parameters [leukocytosis, anemia, elevated lactate dehydrogenase (LDH) values, and splenomegaly]. The aim of this study was to evaluate the prevalence of early/prefibrotic PMF in patients who were previously diagnosed with ET, and to compare clinical features at diagnosis and outcomes between early/prefibrotic PMF and essential thrombocythemia (ET) patients. BM biopsy samples obtained at the time of ET diagnosis were available in 42 patients. Sample reevaluation according to the 2016 revised WHO criteria revealed that early/prefibrotic PMF accounted for 14% of patients who were previously diagnosed with ET, which was comparable to the rates in previous reports. Compared to patients with ET, patients with early/prefibrotic PMF had higher LDH values and higher frequencies of splenomegaly. Overall, myelofibrosis-free and acute myeloid leukemia-free survivals were comparable between the 2 groups. Accurate diagnosis is required to clarify the clinical features of Japanese ET patients.
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Outcome of allogeneic hematopoietic cell transplantation in patients with adult T-cell leukemia
Kamiunten A., Sekine M., Kameda T., Akizuki K., Tahira Y., Shide K., Shimoda H., Kato K., Hidaka T., Kubuki Y., Shimoda K.
Hematological Oncology 36 ( 4 ) 651 - 655 2018年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hematological Oncology
© 2018 The Authors Hematological Oncology Published by John Wiley & Sons Ltd Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell neoplasm, and the outcome of patients with ATL after chemotherapy is poor. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment modality for ATL, and four factors, namely, age > 50 years, male recipient, lack of complete remission at transplantation, and transplantation of cord blood, were previously shown to be associated with poor survival. We retrospectively analyzed the outcome of 21 patients with ATL who had undergone allo-HSCT at our hospital during a 3-year period. Of 21 patients, all had at least one of the above risk factors, and 18 had two or more. With a median follow-up of 19.7 months for living patients, the 1- and 2-year overall survival (OS) rates after transplantation were 34% and 27%, respectively. All relapse/progression events occurred within 1 year after allo-HSCT, and the cumulative incidence of relapse/progression at 1 year after allo-HSCT was 46.9%. The 100-day and 1-year nonrelapse mortality (NRM) rates were 19% and 42%, respectively. No significant difference in OS was observed between myeloablative and reduced-intensity conditioning regimens. The 3-year OS (27%) of ATL patients who received allo-HSCT and who had at least one adverse factor was somewhat poorer than the 3-year OS of 33% identified in a nationwide study of allo-HSCT in ATL patients in Japan. The high relapse/progression and NRM rates are major problems to be solved to achieve better outcome.
DOI： 10.1002/hon.2549
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The clinical impact of human T-lymphotrophic virus type 1 (HTLV-1) infection on the development of adult T-cell leukemia-lymphoma (ATL) or HTLV-1-associated myelopathy (HAM) / atypical HAM after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and renal transplantation. 査読あり
Noriaki Kawano, Shuro Yoshida, Sayaka Kawano, Takuro Kuriyama, Yoshihiro Tahara, Atsushi Toyofuku, Tatsuya Manabe, Atsushi Doi, Soushi Terasaka, Kiyoshi Yamashita, Yuji Ueda, Hidenobu Ochiai, Kousuke Marutsuka, Yoshihisa Yamano, Kazuya Shimoda, Ikuo Kikuchi:
Journal of clinical and experimental hematopathology. 58 ( 3 ) 107 - 121 2018年9月
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Kamiunten A., Shide K., Kameda T., Sekine M., Kubuki Y., Ito M., Toyama T., Kawano N., Marutsuka K., Maeda K., Takeuchi M., Kawano H., Sato S., Ishizaki J., Akizuki K., Tahira Y., Shimoda H., Hidaka T., Yamashita K., Matsuoka H., Shimoda K.
International Journal of Hematology 107 ( 6 ) 681 - 688 2018年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Hematology
© 2018, The Japanese Society of Hematology. Polycythemia vera (PV) and essential thrombocythemia (ET) are associated with life-threatening thrombohemorrhagic events, and disease progression and development of non-hematological malignancies also reduce long-term survival. We retrospectively surveyed thrombohemorrhagic events and overall survival (OS) in 62 PV and 117 ET patients. The cumulative incidences of thrombohemorrhagic events in PV and ET patients were 11.3 and 10.3%, and the incidence rates were 2.42 and 1.85 per 100 person-years. The combined incidence rates of disease progression and development of non-hematological malignancies in PV and ET patients were 1.73 and 1.69 per 100 person-years. The incidence rates of thrombohemorrhagic events in our Japanese PV/ET patients were lower than those reported by most Western studies, but were comparable to those in the largest prospective observational study in ET patients. The combined incidence rates of disease progression and development of non-hematological malignancies were similar between Japanese and Western PV/ET patients. In ET patients, the conventional risk stratification model based on the presence of advanced age or history of thrombosis was useful to predict thrombosis risk, and both the conventional model and the International Prognostic Score of thrombosis in ET based on the above 2 risk factors plus increased leukocyte count could predict poor survival.
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Effect of ruxolitinib therapy on the quality of life of Japanese patients with myelofibrosis. 査読あり
Oritani K, Ohishi K, Okamoto S, Kirito K, Komatsu N, Tauchi T, Handa H, Saito S, Takenaka K, Shimoda K, Okada H, Amagasaki T, Wakase S, Shimozuma K, Akashi K
Current medical research and opinion. 34 ( 3 ) 531 - 537 2018年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma. 査読あり
Kataoka K, Iwanaga M, Yasunaga JI, Nagata Y, Kitanaka A, Kameda T, Yoshimitsu M, Shiraishi Y, Sato-Otsubo A, Sanada M, Chiba K, Tanaka H, Ochi Y, Aoki K, Suzuki H, Shiozawa Y, Yoshizato T, Sato Y, Yoshida K, Nosaka K, Hishizawa M, Itonaga H, Imaizumi Y, Munakata W, Shide K, Kubuki Y, Hidaka T, Nakamaki T, Ishiyama K, Miyawaki S, Ishii R, Nureki O, Tobinai K, Miyazaki Y, Takaori-Kondo A, Shibata T, Miyano S, Ishitsuka K, Utsunomiya A, Shimoda K, Matsuoka M, Watanabe T, Ogawa S
Blood. 131 ( 2 ) 215 - 225 2018年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Sequential Organ Failure Assessment (SOFA) score as a prognostic factor for disseminated intravascular coagulation patients with infectious disease treated with recombinant human soluble thrombomodulin (rhTM) in clinical practice 査読あり
Noriaki Kawano, Akira Tasaki, Sayaka Kawano, Shuro Yoshida, Yoshihiro Tahara, Takuro Kuriyama, Kiyoshi Yamashita, Hidenobu Ochiai, Kazuya Shimoda, Ikuo Kikuchi
Japanese Journal of Transfusion and Cell Therapy. 63 ( 6 ) 763 - 779 2017年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor-Naïve Patients With Myelofibrosis. 査読あり
Mesa RA, Kiladjian JJ, Catalano JV, Devos T, Egyed M, Hellmann A, McLornan D, Shimoda K, Winton EF, Deng W, Dubowy RL, Maltzman JD, Cervantes F, Gotlib J
Journal of clinical oncology. 35 ( 34 ) 3844 - 3850 2017年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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A nationwide survey of hypoplastic myelodysplastic syndrome (a multicenter retrospective study). 査読あり
Kobayashi T, Nannya Y, Ichikawa M, Oritani K, Kanakura Y, Tomita A, Kiyoi H, Kobune M, Kato J, Kawabata H, Shindo M, Torimoto Y, Yonemura Y, Hanaoka N, Nakakuma H, Hasegawa D, Manabe A, Fujishima N, Fujii N, Tanimoto M, Morita Y, Matsuda A, Fujieda A, Katayama N, Ohashi H, Nagai H, Terada Y, Hino M, Sato K, Obara N, Chiba S, Usuki K, Ohta M, Imataki O, Uemura M, Takaku T, Komatsu N, Kitanaka A, Shimoda K, Watanabe K, Tohyama K, Takaori-Kondo A, Harigae H, Arai S, Miyazaki Y, Ozawa K, Kurokawa M, for National Research Group on Idiopathic Bone Marrow Failure Syndromes.
American Journal of hematology. 92 ( 12 ) 1324 - 1332 2017年9月
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Loss of Tyrosine Kinase 2 Does Not Affect the Severity of Jak2V617F-induced Murine Myeloproliferative Neoplasm. 査読あり
Yamaji T, Shide K, Kameda T, Sekine M, Kamiunten A, Hidaka T, Kubuki Y, Shimoda H, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Shimoda K
Anticancer research. 37 ( 7 ) 3841 - 3847 2017年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Prediction of Sustained Virological Response to Telaprevir/Simeprevir-Based Triple Therapy in Patients with Genotype 1 Hepatitis C Virus Using Super-Early Viral Response within 2 Weeks. 査読あり
Ozono Y, Takaishi Y, Tsuchimochi M, Nakamura K, Abe H, Miike T, Kusumoto K, Iwakiri H, Sueta M, Tahara Y, Yamamoto S, Hasuike S, Nagata K, Shimoda K
Journal of Liver. 6 ( 6 ) 1 - 6 2017年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Hmga2 collaborates with JAK2V617F in the development of myeloproliferative neoplasms. 査読あり
Ueda K, Ikeda K, Ikezoe T, Harada-Shirado K, Ogawa K, Hashimoto Y, Sano T, Ohkawara H, Kimura S, Shichishima-Nakamura A, Nakamura Y, Shikama Y, Mori T, Mason PJ, Bessler M, Morishita S, Komatsu N, Shide K, Shimoda K, Koide S, Aoyama K, Oshima M, Iwama A, Takeishi Y
Blood advances. 1 ( 15 ) 1001 - 1015 2017年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Calreticulin mutant mice develop essential thrombocythemia that is ameliorated by the JAK inhibitor ruxolitinib. 査読あり
Shide K., Kameda T., Yamaji T., Sekine M., Inada N., Kamiunten A., Akizuki K., Nakamura K., Hidaka T., Kubuki Y., Shimoda H., Kitanaka A., Honda A., Sawaguchi A., Abe H., Miike T., Iwakiri H., Tahara Y., Sueta M., Hasuike S., Yamamoto S., Nagata K., Shimoda K.
Leukemia. 31 ( 5 ) 1136 - 1144 2017年5月
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Effects of mogamulizumab in adult T-cell leukemia/lymphoma in clinical practice. 査読あり
Sekine M, Kubuki Y, Kameda T, Takeuchi M, Toyama T, Kawano N, Maeda K, Sato S, Ishizaki J, Kawano H, Kamiunten A, Akizuki K, Tahira Y, Shimoda H, Shide K, Hidaka T, Kitanaka A, Yamashita K, Matsuoka H, Shimoda K
European journal of haematology. 98 ( 5 ) 501 - 507 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1111/ejh.12863
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Impact of TET2 Deficiency on Iron Metabolism in Erythroblasts. 査読あり
Inokura K, Fujiwara T, Saito K, Iino T, Hatta S, Okitsu Y, Fukuhara N, Onishi Y, Ishizawa K, Shimoda K, Harigae H
Experimental hematology. 49 56 - 67.e5 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Impact of combinatorial dysfunctions of Tet2 and Ezh2 on the epigenome in the pathogenesis of myelodysplastic syndrome. 査読あり
Hasegawa N, Oshima M, Sashida G, Matsui H, Koide S, Saraya A, Wang C, Muto T, Takane K, Kaneda A, Shimoda K, Nakaseko C, Yokote K, Iwama A
Leukemia. 31 ( 4 ) 861 - 871 2017年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1038/leu.2016.268
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TET2 mutation in diffuse large B-cell lymphoma. 査読あり
Yoko Kubuki, Takumi Yamaji, Tomonori Hidaka, Takuro Kameda, Kotaro Shide, Masaaki Sekine, Ayako Kamiunten, Keiichi Akizuki, Haruko Shimoda, Yuuki Tahira, Kenichi Nakamura, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Mitsue Sueta, Shojiro Yamamoto, Satoru Hasuike, Kenji Nagata, Akira Kitanaka, Kazuya Shimoda
Journal of clinical and experimental hematopathology 56 ( 3 ) 145 - 149 2017年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.3960/jslrt.56.145
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The Impact of a Humanized CCR4 Antibody (Mogamulizumab) on Patients with Aggressive-Type Adult T-Cell Leukemia-Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation. 査読あり
Noriaki Kawano, Takuro Kuriyama, Shuro Yoshida, Sayaka Kawano, Yoshihisa Yamano, Kousuke Marutsuka, Seiichirou Minato, Kiyoshi Yamashita, Hidenobu Ochiai, Kazuya Shimoda, Fumihiko Ishikawa, Ikuo Kikuchi
Journal of clinical and experimental hematopathology 56 ( 3 ) 135 - 144 2017年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.3960/jslrt.56.135
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Differences in Hematological and Clinical Features Between Essential Thrombocythemia Cases With JAK2- or CALR-Mutations. 査読あり
Kubuki Y, Shide K, Kameda T, Yamaji T, Sekine M, Kamiunten A, Akizuki K, Shimoda H, Tahira Y, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Hashimoto K, Yamamoto S, Hasuike S, Hidaka T, Nagata K, Kitanaka A, Shimoda K
Annals of laboratory medicine. 37 ( 2 ) 159 - 161 2017年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Development of a complete human IgG monoclonal antibody to transferrin receptor 1 targeted for adult T-cell leukemia/lymphoma. 査読あり
Shimosaki S, Nakahata S, Ichikawa T, Kitanaka A, Kameda T, Hidaka T, Kubuki Y, Kurosawa G, Zhang L, Sudo Y, Shimoda K, Morishita K
Biochemical and Biophysical Research Communications. 485 ( 1 ) 144 - 151 2017年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Clinical features and outcomes of patients with primary myelofibrosis in Japan: report of a 17-year nationwide survey by the Idiopathic Disorders of Hematopoietic Organs Research Committee of Japan. 査読あり
Takenaka K, Shimoda K, Uchida N, Shimomura T, Nagafuji K, Kondo T, Shibayama H, Mori T, Usuki K, Azuma T, Tsutsumi Y, Tanaka J, Dairaku H, Matsuo K, Ozawa K, Kurokawa M, Arai S, Akashi K
International Journal of Hematology. 105 ( 1 ) 59 - 69 2017年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.3960/jslrt.18032.
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Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis. 査読あり
Komatsu N, Kirito K, Shimoda K, Ishikawa T, Ohishi K, Ohyashiki K, Takahashi N, Okada H, Amagasaki T, Yonezu T, Akashi K
International Journal of Hematology. 105 ( 3 ) 309 - 317 2016年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition. 査読あり
Sashida G, Wang C, Tomioka T, Oshima M, Aoyama K, Kanai A, Mochizuki-Kashio M, Harada H, Shimoda K, Iwama A
The Journal of experimental medicine. 213 ( 8 ) 1459 - 1477 2016年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Clinical Features and Treatment Outcomes of 51 Patients with Chronic Myeloid Leukemia Treated with a Tyrosine Kinase Inhibitor at a Single Institution from 2002 to 2014. 査読あり
Kawano N, Yoshida S, Kawano S, Kuriyama T, Yamashita K, Ochiai H, Shimoda K, Ishikawa F, Ueda A, Kikuchi I
Journal of clinical and experimental hematopathology 56 ( 1 ) 34 - 42 2016年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers. 査読あり
Kataoka K, Shiraishi Y, Takeda Y, Sakata S, Matsumoto M, Nagano S, Maeda T, Nagata Y, Kitanaka A, Mizuno S, Tanaka H, Chiba K, Ito S, Watatani Y, Kakiuchi N, Suzuki H, Yoshizato T, Yoshida K, Sanada M, Itonaga H, Imaizumi Y, Totoki Y, Munakata W, Nakamura H, Hama N, Shide K, Kubuki Y, Hidaka T, Kameda T, Masuda K, Minato N, Kashiwase K, Izutsu K, Takaori-Kondo A, Miyazaki Y, Takahashi S, Shibata T, Kawamoto H, Akatsuka Y, Shimoda K, Takeuchi K, Seya T, Miyano S, Ogawa S
Nature. 534 ( 7607 ) 402 - 406 2016年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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All-trans retinoic acid and interferon-α increase CD38 expression on adult T-cell leukemia cells and sensitize them to T cells bearing anti-CD38 chimeric antigen receptors. 査読あり
Mihara K, Yoshida T, Ishida S, Takei Y, Kitanaka A, Shimoda K, Morishita K, Takihara Y, Ichinohe T
Blood cancer journal. 6 ( 5 ) e421 2016年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Ezh2 regulates the Lin28/let-7 pathway to restrict activation of fetal gene signature in adult hematopoietic stem cells. 査読あり
Oshima M, Hasegawa N, Mochizuki-Kashio M, Muto T, Miyagi S, Koide S, Yabata S, Wendt GR, Saraya A, Wang C, Shimoda K, Suzuki Y, Iwama A
Experimental hematology. 44 ( 4 ) 282 - 296 2016年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Variegated RHOA mutations in adult T-cell leukemia/lymphoma.(共著) 査読あり
Nagata Y, Kontani K, Enami T, Kataoka K, Ishii R, Totoki Y, Kataoka TR, Hirata M, Aoki K, Nakano K, Kitanaka A, Sakata-Yanagimoto M, Egami S, Shiraishi Y, Chiba K, Tanaka H, Shiozawa Y, Yoshizato T, Suzuki H, Kon A, Yoshida K, Sato Y, Sato-Otsubo A, Sanad
Blood 2016年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Splenic irradiation provides transient palliation for symptomatic splenomegaly associated with primary myelofibrosis: a report on 14 patients.(共著) 査読あり
Akira Kitanaka, Katsuto Takenaka, Kotaro Shide, Toshihiro Miyamoto, Tadakazu Kondo, Keiya Ozawa, Mineo Kurokawa, Koichi Akashi, Kazuya Shimoda
International Journal of Hematology 2016年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Clinical Impact of a Humanized CCR4 Antibody (Mogamulizumab) in 14 Patients with Aggressive Adult T-cell Leukemia-lymphoma Treated at a Single Institution During a Three-year Period (2012-2014). 査読あり
Kawano N, Kuriyama T, Sonoda KH, Yoshida S, Yamashita K, Ochiai H, Shimoda K, Ishikawa F, Ueda A, Kikuchi I
Internal medicine. 55 ( 11 ) 1439 - 1445 2016年
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer.(共著) 査読あり
Tadashi Miike, Shojiro Yamamoto, Yoshifumi Miyata, Tomoya Hirata, Yuko Noda, Takaho Noda, Sho Suzuki, Sachiko Takeda, Shuichiro Natsuda, Mai Sakaguchi, Kosuke Maemura, Kanna Hashimoto, Takumi Yamaji, Hiroo Abe, Hisayoshi Iwakiri, Yoshihiro Tahara, Satoru
Gastroenterology Research and Practice 2015年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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TET2 Mutation in Adult T-Cell Leukemia/Lymphoma.(共著) 査読あり
Shimoda K, Shide K, Kameda T, Hidaka T, Kubuki Y, Kamiunten A, Sekine M, Akizuki K, Shimoda H, Yamaji T, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Kitanaka A
J Clin Exp Hematop. 2015年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Resveratrol selectively induces apoptosis in malignant cells with the JAK2V617F mutation by inhibiting the JAK2 pathway.(共著) 査読あり
Trung LQ, Espinoza JL, An DT, Viet NH, Shimoda K, Nakao S
Molecular Nutrition & Food Research 2015年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Integrated molecular analysis of adult T cell leukemia/lymphoma.(共著) 査読あり
Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga J, Totoki Y, Chiba K, Sato-Otsubo A, Nagae G, Ishii R, Muto S, Kotani S, Watatani Y, Takeda J, Sanada M, Tanaka H, Suzuki H, Sato Y, Shiozawa Y, Yoshizato T, Yoshida K, Makishima H, Iwana
Nature Genetics 2015年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Analysis of the molecular mechanism underlying bone marrow necrosis with acute lymphoblastic leukemia.(共著) 査読あり
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 2015年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Two cases of acute hepatitis E infected with descendant strains of hepatitis E virus genotype 3 strain isolated from swine herd in Miyazaki Prefecture 12 years ago - one case had acute facial paralysis.(共著) 査読あり
Tadashi Miike, Shojiro Yamamoto, Yoshifumi Miyata, Tomoya Hirata, Yuko Noda, Takaho Noda, Sho Suzuki, Sachiko Takeda, Shuichiro Natsuda, Mai Sakaguchi, Kosuke Maemura, Kanna Hashimoto, Takumi Yamaji, Hiroo Abe, Hisayoshi Iwakiri, Yoshihiro Tahara, Satoru
Nihon Shokakibyo Gakkai Zasshi. 2015年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Gene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms.(共著) 査読あり
Takuro Kameda, Kotaro Shide, Takumi Yamaji, Ayako Kamiunten, Masaaki Sekine, Tomonori Hidaka, Yoko Kubuki, Goro Sashida, Kazumasa Aoyama, Makoto Yoshimitsu, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Shojiro Yamamoto, Satoru Hasuike, K
Genomics Data 2015年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Clinical Features and Treatment Outcomes of 81 Patients with Aggressive Type Adult T-cell Leukemia-lymphoma at a Single Institution over a 7-year Period (2006-2012).(共著) 査読あり
Noriaki Kawano, Noriaki Kawano, Shuro Yoshida, Takuro Kuriyama, Yoshihiro Tahara, Kiyoshi Yamashita1, Yuri Nagahiro, Jiro Kawano, Hideki Koketsu, Atsushi Toyofuku, Tatsuya Manabe, Kiichiro Beppu, Nobuyuki Ono, Daisuke Himeji, Naoko Yokota-Ikeda, Sanshiro
Internal medicine 2015年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes. (共著) 査読あり
Kenichi Izumi, Keiichiro Mine，Yoshitaka Inoue，Miho Teshima，Shuichiro Ogawa，Yuji Kai，Toshinobu Kurafuji，Kanako Hirakawa，Daiki Miyakawa，Haruka Ikeda，Akari Inada，Manami Hara，Hisakata Yamada，Koichi Akashi，Yoshiyuki Niho，Keisuke Ina，Takashi Kobayashi，Yasunobu
Nature Communications 2015年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator （共著） 査読あり
Kameda T, Shide K, Yamaji T, Kamiunten A, Sekine M, Taniguchi Y, Hidaka T, Kubuki Y, Shimoda H, Marutsuka K, Sashida G, Aoyama K, Yoshimitsu M, Harada ,Abe H, MiikeT,Hisayoshi Iwakiri H,Tahara Y, Sueta M, Yamamoto S,Hasuike S,Nagata K, Iwama A,Kitana
blood 2015年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Primary Central Nervous System Lymphoma in Miyazaki, Southwestern Japan, a Human T-Lymphotropic Virus Type-1 (HTLV-1)-Endemic Area (共著) 査読あり
Maekawa K, Moriguchi-Goto S, Kamiunten A, Kubuki Y, Shimoda K, Takeshima H, Asada Y, Marutsuka K.
Journal of clinical and experimental hematopathology 2014年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Impact of a single nucleotide polymorphism upstream of the IL28B gene in patients positive for anti-HCV antibody in an HCV hyperendemic area in Japan. （共著） 査読あり
Oda K, Uto H, Kumagai K, Ido A, Kusumoto K, Shimoda K, Hayashi K, Stuver SO, Tanaka Y, Nishida N, Tokunaga K, Tsubouchi H
Journal of medical virology 2014年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer (共著) 査読あり
Harada T, Yamamoto E, Yamano HO, Nojima M, Maruyama R, Kumegawa K, Ashida M, Yoshikawa K, Kimura T, Harada E, Takagi R, Tanaka Y,Aoki H, Nishizono M, Nakaoka M, Tsuyada A, Niinuma T, Kai M5, Shimoda K, Shinomura Y, Sugai T, Imai K, Suzuki H
Cancer prevention research (Philadelphia, Pa.) 2014年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer.
Harada T, Yamamoto E, Yamano HO, Nojima M, Maruyama R, Kumegawa K, Ashida M, Yoshikawa K, Kimura T, Harada E, Takagi R, Tanaka Y, Aoki H, Nishizono M, Nakaoka M, Tsuyada A, Niinuma T, Kai M, Shimoda K, Shinomura Y, Sugai T, Imai K, Suzuki H
Cancer prevention research (Philadelphia, Pa.) 7 ( 10 ) 1002 - 10 2014年10月
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Tyk2-dependent bystander activation of conventional and nonconventional Th1 cell subsets contributes to innate host defense against Listeria monocytogenes infection (共著) 査読あり
Hashiguchi T, Oyamada A, Sakuraba K, Shimoda K, Nakayama KI, Iwamoto Y, Yoshikai Y, Yamada H
The Journal of immunology (1950) 2014年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Tyk2 is a therapeutic target for psoriasis-like skin inflammation. (共著) 査読あり
Ishizaki M, Muromoto R, Akimoto T, Sekine Y , Kon S, Diwan M, Maeda H, Togi S, Shimoda K, Oritani K, Matsuda T
International Immunology 2014年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Gastrointestinal bleeding in acutemyeloid leukemia patients receiving intensive induction chemotherapy (共著) 査読あり
Yamamoto S, Miike T, Kubuki Y, Yamaji T, Nakamura K, Abe H, Hashimoto K, Natsuda S, H-Sakaguchi M, Tahara Y, Harada T, Iwakiri H, Hasuike S, Nagata K, Kitanaka A, Matsumoto T, Shimoda K
JSM Gastroenterology and Hepatology 2014年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers. (共著) 査読あり
Nakahata S, Ichikawa T, Maneesaay P, Saito Y, Nagai K, Tamura T, Manachai N, Yamakawa N, Hamasaki M, Kitabayashi I, Arai Y, Kanai Y, Taki T, Abe T, Kiyonari H, Shimoda K, Ohshima K, Horii A, Shima H, Taniwaki M, Yamaguchi R, Morishita K.
Nature communications 2014年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Effects of recombinant human soluble thrombomodulin treatment for disseminated intravascular coagulation at a single institution?an analysis of 62 cases caused by infectious diseases and 30 cases caused by hematological diseases 査読あり
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 53 205 - 213 2014年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Effect of NS-018, a selective JAK2V617F inhibitor, in a murine model of myelofibrosis (共著) 査読あり
Nakaya Y,Shide K, Naito H, Niwa T, Horio T, Miyake J, Shimoda K
Blood cancer journal 2014年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Concurrent of Ezh2 and Tet2 cooperates in the Pathogenesis of myelodysplastic disorders. 査読あり
Muto T, Sashida G, Oshima M, Wendt GR, Mochizuki-Kashio M, Nagata Y, Sanada M, Miyagi S, Saraya A, Kamio A, Nagae G, Nakaseko C, Yokote K, Shimoda K, Koseki H, Suzuki Y, Sugano S, Aburatani H, Ogawa S, Iwama A
Journal of Experimental Medicine 210 ( 12 ) 2627 - 2639 2013年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Jun activation domain-binding protein1(JAB1)is required for the optimal response to interferons 査読あり
Muromoto R, Nakajima M, Hirashima K, Hirao T, Kon S, Shimoda K, Oritani K, Matsuda T
Journal of Biological Chemistry 288 ( 43 ) 30969 - 30979 2013年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Clinical chanracteristics and outcomes of 11 patients with pure redcell aplasia at a single institution over a 13-year period 査読あり
Kawano N, Nagahiro Y, Yoshida S, Yamashita K, Himeji D, Yokota-Ikeda N, Uezono S, Shimao Y, Makino S, Shimoda K. Ueda A
Internal Medicine 52 2025 - 2030 2013年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Contribution of bone marrow-derived hematopoietic stem/progenitor cells to the generation of donor-marker+ cardiomyocytes in vivo 査読あり
Fukata M, Ishikawa F, Najima Y, Yamauchi T, Saito Y, Takenaka K, Miyawaki K, Shimazu H, Shimoda K, Kanemaru T, Nakamura K, Odashiro K, Nagafuji K, Harada M, Akashi K
PLoS One 8 ( 5 ) e62506 2013年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Impact of antibody to hepatitis B core antigen on the clinical course of hepatitis C virus carriers in a hyperendemic area in Japan 査読あり
Tsubouchi N,Uto H, Kumagai K, Sasaki F, Kanmura S, Numata M, Moriuchi A, Oketani M, Ido A, Hayashi K, Kusumoto K, Shimoda K, Stuver SO, Tsubouchi H
Hepatology Research 43 1130 - 1138 2013年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Tyk2 and stat3 regulate brown adipose tissue differentiation and obesity. 査読あり
Derecka M, Gornicka A, Koralov SB, Szczepanek K, Morgan M, Raje V, Sisler J, Zhang Q, Otero D, Cichy J, Rajewsky K, Shimoda K, Poli V, Strobl B, Pellegrini S,Hamis TE, Seale P, Russell AP, McAinch AJ, O’Brien PE, Keller SR, Croniger CM, Kordula T, Lamer A
Cell Metabolism 16 814 - 824 2012年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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TET2 is essential for survival and hematopoietic stem cell homeostasis. 査読あり
Shide K, Kameda T, Shimoda H, Yamaji T, Abe H, Kamiunten A, Sekine M, Hidaka T, Katayose K, Kubuki Y, Yamamoto S, Miike T, Iwakiri H, Hasuike S, Nagata K, Marutsuka K, Iwama A, Matsuda T, Kitanaka A, Shimoda K
Leukemia 26 2216 - 2223 2012年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Potentiated activation of VLA-4 and VLA-5 accelerates proplatelet-like formation. 査読あり
Matsunaga T, Fukai F, Kameda T, Shide K, Shimoda H, Torii E, Kamiunten A, Sekine M,Yamamoto S, Hidaka T, Kubuki Y, Yokokura S, Uemura M, Matsuoka A, Waki F, Matsumoto K, Kanaji N, Ishii T, Imataki O, Dobashi H, Bandoh S, Shimoda K
Annals of Hematology 91 1633 - 1643 2012年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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MATSUNAGA Takuya, YAMASHITA Kiyoshi, KUBUKI Yoko, TOYAMA Takanori, IMATAKI Osamu, MAEDA Kouichi, KAWANO Noriaki, SATOU Seiichi, KAWANO Hiroshi, ISHIZAKI Junzo, YOSHIDA Shuro, KAMEDA Takuro, SASAKI Tadashi, SEKINE Masaaki, KAMIUNTEN Ayako, TANIGUCHI Yasuhiro, HIDAKA Tomonori, KATAYOSE Keiko, K-SHIMODA Haruko, SHIDE Kotaro, YAMAMOTO Shojiro, MORITAKE Hiroshi, NUNOI Hiroyuki, MAKINO Shigeyoshi, KITANAKA Akira, MATSUOKA Hitoshi, SHIMODA Kazuya
International journal of hematology 96 ( 3 ) 342 - 349 2012年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Acute myeloid leukemia in clinical practice: a retrospective population-based cohort study in Miyazaki Prefecture, Japan. 査読あり
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 Hematology 96 342 - 349 2012年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Clinical features and treatment outcomes of isolated secondary central nervous system lymphomas in Miyazaki Prefecture. 査読あり
Kawano N, Ochiai H, Yoshida S, Yamashita K, Shide K, Shimoda H, Hidaka T, Kubuki Y, Katayose K, Toyama T, Kawano H, Matsuoka H, Ishizaki J, Maeda K, Satou S, Yano T, Yamaguchi K, Takenaka K, Shimao Y, Oshima K, Ueda A, Shimoda K
International Journal Clinical Oncology 17 336 - 340 2012年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Difference in serum complement component C4a levels between hepatitis C virus carriers with persistently normal alanine aminotransferase levels or chronic hepatitis C. 査読あり
Imakiire K, UtoH, SatoY, Sasaki F, Mawatari S, Ido A, Shimoda K, Hayashi K, Stuver O. S, Ito Y, Okanoue T, Tsubouchi H
Molecular Medicine Reports 6 259 - 264 2012年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Elevated HIF-1α expression of acute myelogenous leukemia stem cells in the endosteal hypoxic zone may be a cause of minimal residual disease in bone marrow after chemotherapy. 査読あり
Matsunaga T, Imataki O, Torii E, Kameda T, Shide K, Shimoda H, Kamiunten A, Sekine M, Taniguchi Y, Yamamoto S, Hidaka T, Katayose K, Kubuki Y, Dobashi H, Bandoh S, Ohnishi H, Fukai F, Shimoda K.
Leukemia Researchi 36 e122 - 124 2012年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Clinical significance of CADM1/TSLC1/IgSF4 expression in Adult T-cell leukemia/lymphoma. 査読あり
Nakahata S, Saito Y, Marutsuka K, Hidaka T, Maeda K, Hatakeyama K, Shiraga T, Goto A, Takamatsu N, Asada Y, Utsunomiya A, Okayama A, Kubuki Y, Shimoda K, Ukai Y, Kurosawa G, Morishita K
Leukemia 26 1238 - 1246 2012年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Clinical features and outcomes of 35 Disseminated intravascular coagulation cases treated with recombinant human soluble thrombomodulin at a single institution. 査読あり
Kawano N, Yoshida S, Ono N, Himeji D, Nagahiro Y, Kawano S, Yamashita K, Ikeda N,Uezono S, Ochiai H, Kawano F, Kikuchi I, Ishikawa F, Shimoda K, Ueda A, Akashi K
Journal of Clinical and Experimental Hematopathology 51 ( 2 ) 101 - 107 2011年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice. 査読あり
Ishizaki M.Muromoto R, Akimoto T, Ohshiro Y, Takahashi M, Sekine Y, Maeda H, Shimoda K, Oritani K, Matsuda T.
International Immunology 23 ( 9 ) 575 - 582 2011年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Involvement of Tyk2 in both the IL-12/Th1 and IL-23/Th17 axes in vivo. 査読あり
Ishizaki M,Akimoto T, Muromoto R, Yokoyama M, Ohshiro Y, Sekine Y, MaedaH, Shimoda K, Oritani K, Matsuda T
The Journal of Immunology 187 ( 1 ) 181 - 189 2011年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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R723, a selective JAK2 inhibitor, effectively treats JAK2V617F-induced murine myeloproliferative neoplasma. 査読あり
Shide K. Kameda T, Markovtsov V, Shimoda HK, Tonkin E, Fang S, Liu C, Gelman M, Lang W, Romero J, McLaughlim J, Bhamidipati S, Clough J, Low C, Reitsma A, Siu S, Pine P, Park G, Tomeros A, Duan M, Singh R, Payan DG, Matsunaga T, Hitoshi Y, Shimoda K
Blood 117 ( 25 ) 6866 - 6875 2011年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cell. 査読あり
Ryuta Muromoto, et al
European Journal of Immunology 40 ( 12 ) 3570 - 3580 2010年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Tyrosine kinase 2 interacts with the proapoptotic protein Siva-1 and augments its apoptotic functions. 査読あり
Shimoda HK,et al
Biochemical and Biophysical Research Communications 400 ( 2 ) 252 - 257 2010年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Successful treatment of cryoglobulinemic glomerulonephritis derived from Waldenstrom's macroglobulinemia by rituximab-CHOP and tandem high-dose chemotherapy with autologous peripheral blood stem cell transplantation. 査読あり
KawanoNoriaki,et al
International Journal of Hematology 92 ( 2 ) 391 - 397 2010年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Absence of gain-of-function JAK1 and JAK3 mutations in adult T cell leukemia/lymphoma. 査読あり
Kameda Takuro,et al
International Journal of Hematology 92 ( 2 ) 320 - 325 2010年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation. 査読あり
Oku S, et al
British Journal of Haematology 150 ( 3 ) 334 - 344 2010年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Prognostic significance of S-phase kinase-associated protein 2 and p27kip1 in patients with diffuse large B-cell lymphoma: effects of rituximab 査読あり
Seki Ritsuko,et al
Annals of Oncology 21 ( 4 ) 833 - 841 2010年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. （共著） 査読あり
Seki Ritsuko 他
Cancer Science 100 ( 10 ) 1842 - 1847 2009年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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The impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis: a prospective survey of 202 cases in Japan. （共著） 査読あり
Tomonori Hidaka 他
Eur J Haematol 83 ( 4 ) 328 - 333 2009年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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ペグインターフェロン＋リバビリン併用療法における早期HCVコア抗原推移による治療効果予測の検討 （共著） 査読あり
土持舞衣 他
宮崎県医師会医学会誌 33 ( 2 ) 102 - 108 2009年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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VLA-5-mediated adhesion to fibronectin accelerates hemin-stimulated erythroid differentiation of K562 cells through induction of VLA-4 expression. （共著） 査読あり
Rika Tanaka 他
J. Biol. Chem. 284 ( 30 ) 19817 - 19825 2009年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation. （共著） 査読あり
Furuhata Ayako 他
Biochem Biophys Res Commun 383 ( 4 ) 411 - 416 2009年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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急性白血病化学療法後の肺浸潤影 （共著）
下田和哉, 亀田拓郎, 下田晴子, 片寄恵子, 山下清, 幣光太郎, 日高智徳, 久冨木庸子
血液フロンティア 18 ( 10 ) 5 - 10 2008年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Ｃ型慢性肝炎に対するインターフェロンβ投与にて潰瘍性大腸炎が改善した１例 （共著） 査読あり
三池忠, 田原良博, 山口由美, 原田拓, 安倍弘生, 楠元寿典, 沼田政嗣, 蓮池悟, 山本章二朗, 児玉眞由美, 林克裕, 下田和哉
日本消化器病学会雑誌 105 ( 9 ) 1362 - 1366 2008年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Endoscopic characterization of the small bowel in patients with portal hypertension evaluated by double balloon endoscopy. "jointly worked" 査読あり
Mayumi Kodama, Hirofumi Uto, Masatsugu Numata, Takeshi Hori, Takanobu Murayama, Fumisato Sasaki, Naoko Tsubouchi, Akio Ido, Kazuya Shimoda, Hirohito Tsubouchi
J Gastroenterol 43 ( 8 ) 589 - 596 2008年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by gammadelta T cells. "jointly worked" 査読あり
Risa Nakamura, Kensuke Shibata, Hisakata Yamada, Kazuya Shimoda, Keiichi Nakayama and Yoshikai Yasunob
J Immunol. 181 ( 3 ) 2071 - 2075 2008年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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消化器症状を呈した成人Ｔ細胞白血病リンパ腫（ATLL）の１例 （共著） 査読あり
堀川永子, 下田和哉, 瀬戸山充
Skin Cancer 22 ( 3 ) 297 - 302 2008年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Development of ET, primary myelofibrosis, and PV in mice expressing JAK2 V617F. "jointly worked" 査読あり
K Shide, HK Shimoda, TKumano, K Karube, TKameda, K Takenaka, H Abe, S Oku, KS Katayose, K Kusumoto K, S Hasuike, Y Tahara, K Nagata, T Matsuda, K Ohshima, M Hrada, K Shimoda
Leukemia 22 ( 1 ) 87 - 95 2008年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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慢性骨髄増殖性疾患 査読あり
田村和夫、栗山一孝、三浦偉久男、阿南建一、高松泰、下田和哉
臨床と研究 84 ( 10 ) 1451 - 1455 2007年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis 査読あり
Nagafuji K, Nonami A, Kumano T, Kikushige Y, Yoshimoto G, Takenaka K, Shimoda K, Ohga S,Yasukawa M, Horiuchi H, Ishii E, Harada M
Haematologica 92 ( 7 ) 978 - 981 2007年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Chronic thrombopoietin overexpression induces mesangioproliferative glomerulopathy in mice. 査読あり
Shimoda K H, Masahiro Yamamoto,Shide K, Kamezaki K, Matsuda T, Ogawa K, Harada M, Shimoda K
American Journal of Hematology 82 ( 9 ) 802 - 806 2007年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase. 査読あり
Sekine Y, Tsuji S, Ikeda O, Sugiyama K, Oritani K, Shimoda K, Muramoto R, Ohbayashi N, Yoshimura A, Matsuda T
Journal of Immunology 179 ( 4 ) 2397 - 2407 2007年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Tyk2 mutation homologous to V617F Jak2 is not found in essential thrombocythaemia, although it induces constitutive signaling and growth factor independence 査読あり
Shide K, Shimoda K, Kamezaki K, Kakumitsu H, Kumamo T, Numata A, Ishikawa F, Takenaka
Leukemia Research 31 ( 8 ) 1085 - 1092 2007年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Expression of tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γproduction and the induction of Th1 cell differentiation. 査読あり
Tokumasa N, Suto A, Kagami S, Furuta S, Saito Y,Shimoda K, et al
Blood 110 ( 2 ) 553 - 560 2007年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Distinctive expression of myelomonocytic markers and down-regulation of CD34 in acute myelogenous leukaemia with FLT3 tandem duplication and nucleophosmin mutation 査読あり
Mori Y, Yoshimoto G, Kumano T, Miyamoto T, Iino T, Takenaka K, Iwasaki H, Harada N, Kinukawa N, Nagafuji K,Teshima T, Shimoda K, Akashi K, Hrada M
Haematology 79 ( 1 ) 17 - 24 2007年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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The effect of anabolic steroids on anemia in myelofibrosis with myeloid metaplasia: Retrospective analysis of 39 patients in Japan. 査読あり
Shimoda Kazuya, Shide Kotaro, Kamezaki Kenjirou, Okamura Takashi, Harada Naoki, Kinukawa Naoko, Ohyshiki Kazuma, Niho Yoshiyuki, Mizoguchi Hideaki, Omine Mitsuhiro, Ozawa Keiya, Hrada Mine
International Journal of Hematology 85 ( 4 ) 338 - 343 2007年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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若年発症骨原発悪性リンパ腫の一例 査読あり
亀田拓郎、山下清、久冨木庸子、下田和哉
日本リンパ網内系学会会誌 47 81 - 81 2007年5月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Tyk2 signaling in host environment plays an important role in contraction of antigen-specific CD8+ T cells following a microbial infection. 査読あり
"Li Wei,Yamada Hisakata, Yajima Toshiki, Nakagawa Ryusuke, Shimoda Kazuya, Nakayama Keiichi, Yoshikai Yasunobu:
Journal of Immunology 178 ( 7 ) 4482 - 4488 2007年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Autoimmune regulation (AIRE) gene is expressed in human activated CD4+ T-cells and regulated by mitogen-activated protein kinase pathway（共著） 査読あり
Nagafuchi S, Katsuta H, Koyanagi-Katsuta R, Yamasaki S, Inoue Y, Shimoda K, Ikeda Y, Shindo M, Yoshida E, Matsuo T, Ohno Y, Kogawa K, Anzai K, Kurisaki H, Kudoh J, Harada M, Shimizu N
Microbiol. Immunol. 50 ( 12 ) 979 - 987 2006年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Tyk2 Tyrosine Kinase Expression is Required for the Maintenance of Mitochondrial Respiration in Primary pro-B Lymphocytes（共著） 査読あり
Potla R, Koeck T, Wegrzyn J, Cherukuri S, Shimoda K, Baker DP, Wolfman J, Planchon SM, Esposito C, Hoit B, Dulak J, Wolfman A, Stuehr D, Larner AC
Molecular Cellular Biology 26 ( 22 ) 8562 - 8571 2006年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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An important role of Tyk2 in APC function of dendritic cells for priming CD8+ T cells producing IFN-gamma（共著） 査読あり
Aizu K, Li W, Yajima T, Arai T, Shimoda K, Nimura Y, Yoshikai Y
Eur J Immunol 36 ( 11 ) 3060 - 3070 2006年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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ATL development from an HTLV-I carrier after a living-donor liver transplantation（共著） 査読あり
Kawano N, Shimoda K, Ishikawa F, Taketomi A, Yoshizumi T, Shimoda S, Yoshida S, Uozumi K, Shinsuke S, Maehara Y, Harada M
Transplantation 82 ( 6 ) 840 - 843 2006年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Sumoylation of Daxx regulates IFN-induced growth suppression of B lymphocytes and hormone receptor-mediated transactivation（共著） 査読あり
Muromoto R, Ishida M, Sugiyama K, Sekine Y, Oritani K, Shimoda K, Matsuda T
J Immunol 177 ( 2 ) 1160 - 1170 2006年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Related Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3 （共著） 査読あり
Nakajima H, Shibata F, Kumagai H, Shimoda K, Kitamura T
Int J Hematol 84 ( 1 ) 54 - 59 2006年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Activation of Tyk2 and Stat3 is required for the apoptotic actions of IFNβ in primary pro-B cells（共著） 査読あり
Gamero AM, Potla R, Wegrzyn J, Edling A, Shimoda K, Link D, Baker D, Grayson J, Larner AC
J Biol Chem 281 ( 24 ) 16238 - 16244 2006年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Modulation of Toll-like receptor 4 signaling by a novel adaptor protein STAP-2 in macrophages（共著） 査読あり
Sekine Y, Yumioka T, Yamamoto T, Muromoto R, Imoto S, Sugiyma K, Oritani K, Shimoda K, Minoguchi M, Akira S, Yoshimura A, Matsuda T
J. Immunol. 176 ( 1 ) 380 - 389 2006年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion（共著） 査読あり
Ishikawa F, Shimazu H, Shultz LD, Fukata M, Nakamura R, Lyons B, Shimoda K, Shimoda S, Kanemaru T, Nakamura K, Ito H, Kaji Y, Perry AC, Harada M
FASEB J 20 ( 7 ) 950 - 952 2006年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Physical and functional interactions between Daxx and STAT3（共著） 査読あり
Muromoto R, Nakao K, Watanabe T, Sato N, Sekine Y, Sugiyama K, Oritani K, Shimoda K, Matsuda T
Oncogene 25 ( 14 ) 2131 - 2136 2006年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）