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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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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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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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Takenaka K., Ito T., Komatsu N., Yamaguchi H., Kirito K., Tomita A., Togano T., Tanaka T., Sugimoto Y., Murai K., Wada H., Kurokawa T., Koike M., Gotoh A., Maekawa T., Kubuki Y., Akagi T., Yamauchi T., Edahiro Y., Ikeda K., Kondo T., Tanaka H., Miyazaki Y., Saito T.I., Shimoda K., Kada A., Saito A.M., Kiyoi H., Akashi K., Matsumura I., Takaori A.
International Journal of Hematology 2026
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Myeloproliferative neoplasms (MPNs) are clonal hematologic disorders characterized by proliferation of one or more myeloid lineages. Data from large-scale prospective studies in Japan remain limited. We conducted a multicenter, prospective observational study (MPN-15) for the Japanese Society of Hematology to assess clinical characteristics, mutation profiles, risk stratification, and treatment patterns of patients diagnosed with polycythemia vera (PV), essential thrombocythemia (ET), prefibrotic primary myelofibrosis (pre-PMF), and fibrotic PMF after 2016. A total of 1252 patients were enrolled (PV: 323; ET: 726; MF: 203). JAK2V617F mutations were detected in 96.8% of PV patients and approximately 60% of patients with other subtypes; CALR and MPL mutations were more common in ET, pre-PMF, and fibrotic PMF. Chromosomal abnormalities and symptom burden were highest in fibrotic PMF. Thrombotic and survival risk stratification revealed that most patients with PV and ET were high risk. Use of ruxolitinib was reported in 14% of PV and 34% of fibrotic PMF patients, with no serious adverse events. This study represents the first large-scale prospective MPN registry in Japan. Ongoing follow-up will provide critical insights into long-term outcomes and therapeutic optimization in the Japanese population.
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Inano T., Sugimoto Y., Ohishi K., Gotoh A., Ito T., Ichii M., Shimoda K., Lin S., Zagrijtschuk O., Qin A., Sato M., Kawase H., Sato T., Komatsu N., Kirito K.
International Journal of Hematology 2026
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Ropeginterferon alfa-2b, a monopegylated interferon α-2b, is a cytoreductive treatment for polycythemia vera (PV). In Japan, the current regimen involves titration in 50-µg increments every 2 weeks until reaching the maximum dose (500 µg), which requires considerable time. This phase 3b, open-label, single-arm, multicenter study (October 2023–July 2024) assessed the efficacy and safety of a three-step dose escalation regimen (day 1: 250 µg, week 2: 350 µg, week 4: 500 µg) of ropeginterferon alfa-2b in Japanese patients with PV (NCT06002490). Twenty-one patients were included (mean age: 57 years); most (95.2%) received ropeginterferon alfa-2b for at least 24 weeks. The complete hematologic response rate (primary endpoint; hematocrit < 45%, no phlebotomy in the previous 12 weeks, platelet count ≤ 400 × 10<sup>9</sup>/L, and white blood cell count ≤ 10 × 10<sup>9</sup>/L) was 23.8% (95% confidence interval 8.2, 47.2) at week 12 and 57.1% (34.0, 78.2) at week 24. Most patients (90.5%) reached the maximum dose of 500 µg by week 4. All patients had treatment-emergent adverse events, but none led to death, treatment discontinuation, or study withdrawal. This three-step dose escalation regimen of ropeginterferon alfa-2b has the potential to provide faster therapeutic effects in patients with PV without additional safety concerns.
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Shimoda K., Takenaka K., Kitamura H., Dohi K., Yoshimoto R., Kirito K.
International Journal of Hematology 2026
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Polycythemia vera (PV) is a myeloproliferative neoplasm that is treated according to the patient’s thrombosis risk, including cytoreductive therapies for those at high-risk for thrombosis. Ropeginterferon alfa-2b, a mono-pegylated interferon α-2b, is a new cytoreductive therapy for PV. This expert consensus study, conducted before ropeginterferon alfa-2b recommendations were added to the Japanese guidelines, used a four-phase Delphi method to survey 18 Japanese hematology experts and develop suggestions for ropeginterferon alfa-2b use in Japan. Several scenarios where ropeginterferon alfa-2b treatment is considered appropriate for patients with PV were identified, including: 1) low-risk patients requiring cytoreductive therapy (excluding low-risk patients requiring cytoreductive therapy due to splenomegaly); 2) patients intolerant or resistant to hydroxyurea treatment; 3) high-risk patients aged ≤ 70 years, even if hematocrit < 45% is achieved and maintained under hydroxyurea treatment; and 4) patients who wish to conceive or who are pregnant and require cytoreductive therapy. This is the first expert consensus study using the Delphi method to examine cytoreductive therapy for Japanese patients with PV and contributes to the appropriate selection of patients for ropeginterferon alfa-2b in clinical practice.
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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診療ガイドラインat a glance 造血器腫瘍診療ガイドライン第3.1版(2024年改訂版)
尾崎 修治、下田 和哉、 日本血液学会造血器腫瘍診療ガイドライン委員会
日本内科学会雑誌 114 ( 12 ) 2278 - 2284 2025.12
Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：(一社)日本内科学会
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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)
Presentations 【 display / non-display 】
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ATL新規治療標的同定と、個別化医療への展開
下田和哉
令和7年度AMED革新がん領域1全体会議 (東京都) 2025.7.26 日本医療研究開発機構研究費 （革新的がん医療実用化研究）
Event date： 2025.7.26
Presentation type：Oral presentation (general)
Venue：東京都
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後期高齢者に対するSGLT2阻害薬の使用実態と安全性についての多施設共同後方視的コホート研究
内田泰介、上野浩晶、小永田綾香、中村孝之、古郷芙未子、鍋倉弘樹、田中友梨、上平雄大、山口秀樹、下田和哉：
第67回日本老年医学会学術集会 (千葉市) 2025.6.27 杏林大学医学部高齢医学教室
Event date： 2025.6.27 - 2025.6.29
Presentation type：Poster presentation
Venue：千葉市
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BRAFV600E変異陽性甲状腺乳頭癌の加療中に発生したBRAFV600E変異陰性甲状腺未分化癌の1剖検例
内田泰介、山口秀樹、菊池幸、別府拓海、積島愛加理、積島宏昂、古郷芙未子、鍋倉弘樹、与那嶺真一、上平雄大、上野浩晶、田中智章、盛口清香、山下篤、下田和哉：
第98回日本内分泌学会学術総会 (千葉市) 2025.6.6 千葉大学大学院医学研究院 内分泌代謝・血液・老年内科学
Event date： 2025.6.5 - 2025.6.7
Presentation type：Oral presentation (general)
Venue：千葉市 Country：Japan
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放射性ヨウ素内用療法後に甲状腺中毒症が遷延したバセドウ病の1例
別府拓海、鍋倉弘樹、内田泰介、菊池幸、古郷芙未子、積島愛加理、与那嶺真一、上平雄大、上野浩晶、寺田珠沙、東美菜子、山口秀樹、下田和哉：
第98回日本内分泌学会学術総会 (千葉市) 2025.6.5 千葉大学大学院医学研究院 内分泌代謝・血液・老年内科学
Event date： 2025.6.5 - 2025.6.7
Presentation type：Poster presentation
Venue：千葉市
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腹部外科術後のショックバイタルを契機に発見された医原性副腎不全の1例
菊池幸、古郷芙未子、別府拓海、積島愛加理、鍋倉弘樹、内田泰介、与那嶺真一、上平雄大、上野浩晶、山口秀樹、下田和哉：
第98回日本内分泌学会学術総会 (千葉市) 2025.6.5 千葉大学大学院医学研究院 内分泌代謝・血液・老年内科学
Event date： 2025.6.5 - 2025.6.7
Presentation type：Poster presentation
Venue：千葉市
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