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医学部 医学科 内科学講座血液・糖尿病・内分泌内科学分野 |
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Shimazu Y., Kameda T., Kitawaki T., Kamiunten A., Sekine M., Kawano H., Sato S., Maeda K., Toyama T., Kawano N., Yamashita K., Takeuchi M., Ishizaki J., Shimoda K., Takaori-Kondo A.
Clinical Immunology 282 2026年1月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical Immunology
Background: Mogamulizumab, an anti-CCR4 monoclonal antibody, is approved for relapsed/refractory (r/r) aggressive adult T-cell leukemia/lymphoma (ATL), although durable responses are limited. Objective: To identify biomarkers associated with mogamulizumab efficacy, focusing on host immune status and known prognostic factors. Methods: We retrospectively analyzed 315 patients with r/r aggressive ATL using real-world data from Japan. Clinical and prognostic variables were analyzed for association with overall survival (OS), stratified by mogamulizumab use. Results: Among 315 patients, 97 received mogamulizumab (Moga [+]). One-year OS was higher in Moga (+) than Moga (−) patients (51.2 % vs. 34.0 %, p = 0.006). Multivariate analysis identified age < 70, PS 0–1, cCa < 11 mg/dL, albumin ≥3.5 g/dL, LDH < 265 IU/L, LMR ≥ 2.6, and Moga (+) use as independent predictors of OS. In Moga (+) patients, cCa and LMR remained independent prognostic factors. Conclusion: LMR is a novel prognostic factor in r/r ATL and may provide useful information when considering mogamulizumab-based treatment.
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幣 光太郎, 亀田 拓郎, 内田 泰介, 上運天 綾子, 秋月 渓一, 久冨木 庸子, 池田 良磨, 宇都 倫史, 深谷 知宏, 三苫 修也, 佐藤 克明, 上平 雄大, 上野 浩晶, 山口 秀樹, 下田 和哉
Blood Neoplasia 2 ( 3 ) 100087 2025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：Elsevier BV
Interferon-α (IFN-α) exhibits antiviral and antiproliferative effects on normal and neoplastic cells. Intracellular signaling of IFN-α is mediated by tyrosine kinase 2 (TYK2) and janus kinase 1 (JAK1), followed by signal transducers and activators of transcription (STATs). TYK2 is redundant for the antiviral effect of IFN-α; however, the requirements for antiproliferative effects are unknown. We assessed the role of TYK2 in the effects of IFN-α in myeloproliferative neoplasm (MPN) model mice. Jak2V617F transgenic mice develop MPNs resembling human primary myelofibrosis, and ropeginterferon-α-2b ameliorated their features. However, these IFN-α effects were absent in Jak2V617F;Tyk2−/− mice. In mixed wild-type (WT)/Jak2V617F chimeric mice, IFN-α treatment induces Jak2V617F hematopoietic stem cells (HSCs) to enter the cell cycle and skew their differentiation into the megakaryocyte lineage, decreasing the number of Jak2V617F HSCs. The effects of IFN-α on Jak2V617F HSCs were not observed in mixed WT/Jak2V617F;Tyk2−/− mice, indicating that TYK2 is essential for the effects of IFN-α on both Jak2V617F progenitors and HSCs. The mechanism of IFN-α in Jak2V617F HSCs and progenitors differed: genes regulating the cell cycle were enriched in IFN-α–stimulated Jak2V617F HSCs, but not in Jak2V617F progenitors; genes regulating antiproliferation were enriched in IFN-α–stimulated Jak2V617F progenitors but not in Jak2V617F HSCs. The major IFN-α signaling molecule activated by JAKs is STAT1, which is essential for the antiviral effect. Most effects of IFN-α on Jak2V617F cells were preserved in Jak2V617F;Stat1−/− mice but to a moderate degree compared with Jak2V617F mice. Our study reveals essential roles of TYK2 for the preferential suppressive effect of IFN-α on Jak2V617F progenitors and HSCs.
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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 122 ( 1 ) 83 - 92 2025年
担当区分：筆頭著者 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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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 ) 2024年12月
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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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 2024年
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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宮崎県における再発/難治性ATLに対するValemetostat療法の治療効果
上運天 綾子
第10回HTLV1学会学術集会 2024年11月10日
開催年月日： 2024年11月8日 - 2024年11月10日
記述言語：日本語 会議種別：口頭発表（一般）
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Retrospective analysis of hematopoietic stem cell transplantation for ATL in University of Miyazaki
上運天 綾子
第86回日本血液学会学術集会 2024年10月13日
開催年月日： 2024年10月11日 - 2024年10月13日
記述言語：日本語 会議種別：ポスター発表
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日常診療における再発/難治性ATLに対するTucidinostat療法の治療効果
上運天 綾子
第9回HTLV1学会学術集会 2023年11月12日
開催年月日： 2023年11月10日 - 2023年11月12日
記述言語：日本語 会議種別：口頭発表（一般）
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Loss of EZH2 does not affect the severity of murine myeloproliferative neoplasms with CALR mutation
上運天 綾子
第83回日本血液学会学術集会 2021年9月24日
開催年月日： 2021年9月23日 - 2021年9月25日
記述言語：日本語 会議種別：口頭発表（一般）
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Development of MALT1 inhibitor and its effect on ATL
上運天 綾子
第82回日本血液学会学術集会 2020年10月10日
開催年月日： 2020年10月10日 - 2020年11月8日
記述言語：日本語 会議種別：口頭発表（一般）
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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骨髄増殖性腫瘍におけるエピゲノム異常の役割
研究課題/領域番号：19K17834 2019年04月 - 2022年03月
科学研究費補助金 若手研究
担当区分：研究代表者