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Faculty of Medicine School of Medicine Department of Internal Medicine, Hematology, Diabetes, and Endocrinology |
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SHIMODA Kazuya
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Degree 【 display / non-display 】
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博士（医学） ( 1994.5 九州大学 )
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医学士 ( 1987.3 九州大学 )
Research Areas 【 display / non-display 】
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Life Science / Hematology and medical oncology
Papers 【 display / non-display 】
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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 110616 2026.1
Language：English Publishing type：Research paper (scientific journal) Publisher：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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Tahira Y., Shide K., Kameda T., Uchida T., Kamiunten A., Akizuki K., Kubuki Y., Karasawa M., Ikeda R., Matsumoto K., Bai J., Terashima M., Kato K., Uto T., Fukaya T., Mitoma S., Sato K., Uehira Y., Ueno H., Sashida G., Yamaguchi H., Shimoda K.
Blood Neoplasia 2 ( 3 ) 100087 2026.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Blood Neoplasia
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<sup>−/−</sup> 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<sup>−/−</sup> 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<sup>−/−</sup> 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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Mesa R., Gill H., Zhang L., Jin J., Kirito K., Komatsu N., Qin A., Xiao Z., Tashi T., Shimoda K., Ohishi K., Chen S., Zuo X., Shirane S., Hu Y., Zhang S., Wang Y., Takenaka K., Ichii M., Xu N., Shih L.Y., Lim K.H., Lee S.E., Bae S.H., Teo W.Z.Y., Maze D., Oh S.T., Bose P., Sato T., Zagrijtschuk O., Lin S., Shih W.J., Mascarenhas J., Masarova L.
Lancet Haematology 12 ( 11 ) e862 - e875 2025.11
Language：English Publishing type：Research paper (scientific journal) Publisher：Lancet Haematology
Background The initial therapy for high-risk essential thrombocythaemia is usually hydroxyurea, but about a third of patients develop intolerance or resistance. A standard second-line agent has been anagrelide. Ropeginterferon alfa-2b, a new-generation interferon-based therapy, is approved for polycythaemia vera. We aimed to assess efficacy and safety of ropeginterferon alfa-2b compared with anagrelide in patients with essential thrombocythaemia with leukocytosis who are intolerant or resistant to hydroxyurea. Methods The SURPASS ET open-label, randomised, active-controlled, phase 3 trial was done at 55 clinical sites across China, Japan, Taiwan, Hong Kong, South Korea, the USA, Singapore, and Canada and enrolled patients aged 18 years and older with high-risk (age >60 years with JAK2 Val617Phe or a history of disease-related thrombosis or haemorrhage), hydroxyurea-intolerant or hydroxyurea-resistant essential thrombocythaemia and white blood cell (WBC) count greater than 10 × 10<sup>9</sup> cells/L. Patients were randomly assigned (1:1) to ropeginterferon alfa-2b or anagrelide, stratified by platelet count, symptom score, and country. Ropeginterferon alfa-2b was subcutaneously dosed every 2 weeks, initially at 250 μg, then titrated to 350 μg at week 2, and to 500 μg from week 4 onward. Anagrelide was orally dosed according to the US Food and Drug Administration-approved prescribing information. The primary endpoint was the rate of response at months 9 and 12, as per modified European LeukemiaNet (ELN) criteria. The main planned analysis for the study was done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT04285086 and is completed, and an extension study for collecting long-term data is ongoing. Findings Between Aug 25, 2020, and Nov 12, 2024, 245 patients were screened and 174 were randomly assigned (91 to ropeginterferon alfa-2b and 83 to anagrelide). The median follow-up was 12·5 months (IQR 11·5–12·9). At baseline, 47 (52%) of 91 participants in the ropeginterferon alfa-2b group and 44 (53%) of 83 participants in the anagrelide group were female. 167 (96%) of 174 participants were Asian and seven (4%) were White. The trial met its primary endpoint, with 39 (43%) of 91 participants in the ropeginterferon alfa-2b group showing durable modified ELN criteria responses at months 9 and 12, compared with five (6%) of 83 participants in the anagrelide group. This difference (36·5%, 95% CI 25·4–47·7) was significant (p=0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 27 (34%) of 80 patients in the anagrelide group and 21 (23%) of 91 patients in the ropeginterferon alfa-2b group. In the ropeginterferon alfa-2b group, the most common grade 3 or worse adverse events were infections and infestations, occurring eight (9%) of 91 patients, compared with five (6%) of 80 patients in the anagrelide group. In the anagrelide group, the most frequent grade 3 or worse adverse events were nervous system disorders, occurring in six (8%) of 80 patients, compared with one (1%) of 91 patients with ropeginterferon alfa-2b. Serious adverse events occurred in 24 (30%) of 80 participants in the anagrelide group and 13 (14%) of 91 participants in the ropeginterferon alfa-2b group). The most common serious adverse event was cerebral infarction, which occurred in four (5%) of 80 patients in the anagrelide group but was not observed in the ropeginterferon alfa-2b group. There were no treatment-related deaths in either study group. Interpretation Our findings suggest that ropeginterferon alfa-2b could be considered as a second-line treatment option for patients with essential thrombocythaemia and leukocytosis. Funding PharmaEssentia.
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Effects of tucidinostat in adult T-cell leukemia/lymphoma in clinical practice Reviewed
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 2025.7
Language：English Publishing type：Research paper (scientific journal) Publisher：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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Post-Diagnosis Hemorrhagic Events Are Strongly Associated With Poor Survival in Patients With Essential Thrombocythemia. Reviewed
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 TI, Kada A, Saito AM, Shimoda K, Sugimoto Y, Kurokawa T, Tomita A, Edahiro Y, Kiyoi H, Akashi K, Matsumura I, Takenaka K, Komatsu N
EJHaem 6 ( 4 ) e70103 2025.7
Books 【 display / non-display 】
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イヤーノート2026 内科・外科編
下田和哉 他（ Role： Joint author , 血液学総論（造血幹細胞移植~脾摘術）、白血球系の異常(白血球増加症～骨髄異形成症候群)、白血球系の異常（悪性リンパ腫以外の成熟B細胞腫瘍～成熟T細胞腫瘍））
株式会社メディックメディア 2025.3
Book type：Scholarly book
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WHO分類第5版による白血病・リンパ系腫瘍の病態学
久冨木庸子、下田和哉 他（ Role： Contributor , 骨髄性／リンパ性腫瘍）
中外医学社 2024.12
Book type：Scholarly book
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イヤーノート2025 内科・外科編
下田和哉 他（ Role： Joint author , 血液学総論（造血幹細胞移植~脾摘術）、白血球系の異常(白血球増加症～骨髄異形成症候群)、白血球系の異常（悪性リンパ腫以外の成熟B細胞腫瘍～成熟T細胞腫瘍））
株式会社メディックメディア 2024.3
Book type：Scholarly book
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別冊日本臨牀 血液症候群（第3版）ーその他の血液疾患を含めてーⅣ
亀田拓郎、幣光太郎、下田和哉（ Role： Joint author , 本態性血小板血症）
株式会社 日本臨牀社 2024.2
Responsible for pages：27-32頁 Language：Japanese Book type：Scholarly book
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血液専門医テキスト(改訂第4版)
下田和哉 他（ Role： Joint author , その他の骨髄増殖性疾患 252-254頁）
株式会社 南江堂 2023.10
Language：Japanese Book type：Textbook, survey, introduction
MISC 【 display / non-display 】
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RINKETSU Dictionary 骨髄線維症に対する新規JAK阻害薬momelotinib
下田和哉
臨床血液 66 ( 7 ) 727 2025.7
Publishing type：Rapid communication, short report, research note, etc. (scientific journal)
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第5土曜特集 マルチオミクスが解き明かす疾患の本質--統合的アプローチによる新たな知見 疾患別マルチオミクス解析の最新動向 【がん】 マルチオミクス解析による血液がんの病態解明と臨床への展開
亀田 拓郎, 下田 和哉
医学のあゆみ 293 ( 9 ) 804 - 810 2025.5
Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：医歯薬出版
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骨髄線維症に対するruxolitinibとmomelotinibの有効性と位置づけ
幣光太郎、下田和哉
血液内科 90 ( 5 ) 553 - 559 2025.5
Publishing type：Rapid communication, short report, research note, etc. (scientific journal)
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【新・白血病学(上)-病態・診断・診療-】白血病の発症と病態形成 白血病の染色体異常・遺伝子異常と病態形成機構 各論 骨髄増殖性腫瘍の分子病態
長嶺宏士朗、下田和哉
日本臨床 83 ( 増刊4 ) 2025.4
Publishing type：Rapid communication, short report, research note, etc. (scientific journal)
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特集 白血病･リンパ腫 臨床現場で役立つ白血病･リンパ腫の最新の知識 さまざまな白血病･リンパ腫病型における診療のポイント 骨髄増殖性腫瘍の診断と治療
亀田 拓郎, 下田 和哉
Medical Practice 42 ( 2 ) 219 - 223 2025.2
Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：(株)文光堂
Presentations 【 display / non-display 】
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Phase I Safety Study of Anti-Transferrin Receptor 1 Antibody (PPMX-T003) in Patients with Polycythemia Vera and Erythrocythemia. International conference
Tomoki Ito, MD, PhD ,Teruhito Takakuwa, MD, PhD , Masayuki Hino, MD, PhD , Hirohisa Nakamae, MD, PhD , Kazunori Murai, MD, PhD , Yoko Kubuki, MD, PhD , Kazuya Shimoda, M.D., Ph.D. , Yuji Kumagai, MD, PhD , Yukiya Yamamoto, MD, PhD and Tadashi Matsuura, PhD:
The American society of Hematology 66th Annual Meeting and Exposition 2024.12.9
Event date： 2024.12.7 - 2024.12.10
Presentation type：Oral presentation (general)
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1805 Impact of Cooperating Myeloid Gene Mutations on Disease Progression and Survival in Japanese MPN Patients: A Multicenter Study. International conference
Saki Ogawa, Kotaro Shide, Masami Takeuchi, Kosei Matsue, Takuro Kameda, Masato Yasumi, Takahiro Karasuno, Taizo Shimomura, Hitoshi Suzushima, Kiyoshi Yamashita, Noriaki Kawano, Osamu Imataki, Norimitsu Kadowaki, Akihito Yonezawa, Eiichi Otsuka, Yoshio Saburi, Yuki Tahira, Ayako Kamiunten, Keiichi Akizuki, Masayoshi Karasawa, Ryoma Ikeda, Kengo Matsumoto, Ayuka Kuroki, Koshiro Nagamine, Yoko Kubuki, Kazuya Shimoda:
The American society of Hematology 66th Annual Meeting and Exposition 2024.12.7
Event date： 2024.12.7 - 2024.12.10
Presentation type：Poster presentation
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腸内細菌叢に由来するコハク酸セミアルデヒドは ATL 細胞の増殖を促進する
千葉 のどか、鈴木 真也、Enriquez-Vera Daniel、宇都宮 與、久冨木 庸子、日髙 智徳、下田 和哉、中畑 新吾、山田 拓司、森下 和広
第10回日本HTLV-1学会学術集会 (東京都) 2024.11.9 東京大学大学院 新領域創成科学研究科 病態医療科学分野
Event date： 2024.11.8 - 2024.11.10
Presentation type：Oral presentation (general)
Venue：東京都
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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、亀田 拓郎、長嶺 宏士朗、黒木 安優香、池田 涼馬、松本 健吾、秋月 渓一、関根 雅明、河野 浩、久冨木 庸子、山下 清、外山 孝典、佐藤 誠一、前田 宏一、石崎 淳三、下田 和哉
第10回日本HTLV-1学会学術集会 (東京都) 2024.11.10 東京大学大学院 新領域創成科学研究科 病態医療科学分野
Event date： 2024.11.8 - 2024.11.10
Presentation type：Oral presentation (general)
Venue：東京都
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HTLV-1 キャリアにおける新型コロナウイルスワクチン接種回数の最適化
亀田 拓郎、宇都宮 與、中野 伸亮、徳永 雅仁、宮園 卓宜、伊藤 能清、米倉 健太郎、日髙 道弘、河北 敏郎、幣 光太郎、田平 優貴、秋月 渓一、上運天 綾子、久冨木 庸子、下田 和哉
第10回日本HTLV-1学会学術集会 (東京都) 2024.11.9 東京大学大学院 新領域創成科学研究科 病態医療科学分野
Event date： 2024.11.8 - 2024.11.10
Presentation type：Poster presentation
Venue：東京都
Awards 【 display / non-display 】
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日本白血病研究基金 清水賞
2002.11 日本白血病研究基金
下田和哉
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
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日本癌学会奨励賞
2002.10 日本がん学会
下田和哉
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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新規病態：HTLV-1陽性HRS細胞を伴う成人T細胞白血病/リンパ腫の統合的解析
Grant number：23K27384 2023.04 - 2027.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(B)
Authorship：Coinvestigator(s)
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新規病態：HTLV-1陽性HRS細胞を伴う成人T細胞白血病/リンパ腫の統合的解析
Grant number：23H02693 2023.04 - 2027.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
Authorship：Coinvestigator(s)
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腫瘍性fibrocyteの本態解明と、骨髄線維症診断・治療への展開
Grant number：23K27629 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(B)
Authorship：Principal investigator
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腫瘍性fibrocyteの本態解明と、骨髄線維症診断・治療への展開
Grant number：23H02938 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
Authorship：Principal investigator
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1007創薬に向けた、CALR変異とfibrocyteに着目する骨髄増殖性腫瘍研究
Grant number：17H04210 2017.04 - 2019.03
科学研究費補助金 基盤研究(B)
下田和哉、久冨木庸子、日髙智徳、幣光太郎
Authorship：Principal investigator
骨髄増殖性腫瘍(MPN)のドライバー変異であるJAK2,CALR変異が同定されMPNの病態が明らかにされつつあるが、CALR変異がMPNを発症させる機序や、骨髄線維症の本態である骨髄線維化細胞の起源、つまり間質の反応性変化なのか、あるいは腫瘍クローン由来fibrocyteなのかは不明である。本研究では以下の3つの方法により、MPNの新たな治療につながる研究を行う。
Ⅰ. MPLとの会合やSTAT活性化に必須な変異CALRの領域同定と、その阻害による治療開発
Ⅱ. 本態性血小板血症から骨髄線維症へ進展する分子イベントの同定
Ⅲ. 腫瘍クローン由来fibrocyteが骨髄線維化に果たす役割の同定と、骨髄線維化を改善することをすでに見出しているMEK阻害剤がfibrocyteに及ぼす影響の解明
Past consigned research fund received 【 display / non-display 】
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A Phase 2b Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Oral HBI-8000 in Patients with Relapsed or Refractory Adult T Cell Lymphoma(ATL)
2017.01 - 2019.12
Investigational New Drug Test
Consigned research type：Investigational New Drug Test
Available Technology 【 display / non-display 】
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骨髄増殖性腫瘍、病因遺伝子の機能解析と新規治療法開発
白血病細胞のゲノム情報に基づく成人T細胞白血病の克服戦略Home Page： 内科学講座 血液・糖尿病・内分泌学分野
Related fields where technical consultation is available：・血液疾患マウスモデルの作成と解析、治療法開発への応用
・サイトカインシグナル伝達機構の解析
（共同研究が可能なテーマ）骨髄増殖性腫瘍、成人T細胞白血病を対象とした研究