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血液内科学／内科学教室（血液内科学部門）

血液内科学　http://www.kpum-hematology.net

大学院科目名 血液内科学
教室名 内科学教室(血液内科学部門)
スタッフ
教授　　黒田　純也
准教授（兼務）　志村　勇司（輸血・細胞医療部）
助教（学内講師）塚本　拓
助教　　　　　　藤野　貴大
助教　　　　　   木元　弥生
研究内容
当教室では「臨床に役立つ血液・腫瘍学研究」をモットーに、以下の基礎・臨床横断断的な研究プロジェクトを展開中です。
 
1. 難治性・治療抵抗性B細胞リンパ腫の病態形成メカニズムの解明による新規治療開発　
「高悪性度B細胞性リンパ腫の分子病態の解明による新規診断法と分子標的治療の開発」、「高リスク濾胞性リンパ腫の臨床診断と分子細胞遺伝学的背景の解明」、「マントル細胞リンパ腫の分子病態解析に基づく新規分子標的治療戦略の開発」を主たるテーマとし、簡便・迅速、しかし論理的な診断システムと新規治療戦略の開発を目指した研究を進めています。
 
難治性造血器腫瘍である多発性骨髄腫(MM)の病態形成や治療抵抗性には、極めて多彩で複雑な分子異常が複雑に絡み合っており、症例間での不均一性も高度であることが治療戦略開発を困難にする要因となっています。その打開を目指して、我々は「細胞遺伝学的・分子生物学的に多様で不均一なMMにおける普遍的な異常の同定」、「多段階悪性化を促進する分子異常・分子制御異常の同定」の両面からのアプローチでの挑戦を継続しています。
 
MMや悪性リンパ腫において腫瘍免疫監視機構の破綻を、より容易に解除しうる治療戦略の開発の実現を目指した研究を推進中です。なかでも、私たちが注目しているのは、「骨髄由来抑制系細胞(MDSC)」です。腫瘍環境においてMDSCが誘導される分子メカニズムの解明を包括的御オミックス解析で紐解き、その制御戦略の開発研究を進めています
 
腫瘍環境誘導性の治療抵抗性獲得機序の解明を通じ、難治病態克服戦略開発のための研究を行っています。
 
京都府立医科大学血液内科学教室と同門会所属組織は、「京都血液臨床研究グループ(KOTOSG)」を構成し、血液診療に関わる様々なリアルワールドの課題の解決に挑戦するとともに、希少病態の情報共有を推進し、日常診療への活用と研究シーズの探索を進めています。
 
研究業績
  1. Ide D, Yokoo H, Mizutani S, Inoue Y, Okamoto H, Tsukamoto T, Demizu Y, Shimura Y, Oba M, Kuroda J. Synthesis and Evaluation of a Potential RSK2 Degrader in Human Multiple Myeloma Cell Lines. Chem Pharm Bull, 74:240-246, 2026.
  2. Ito K, Okamoto H, Maekura C, Fujino T, Tsukamoto T, Mizutani S, Shimura Y, Kuroda J. Pseudoprogression of bladder extramedullary disease of multiple myeloma following the treatment with elranatamab, an anti-BCMA/CD3 bispecific antibody. J Clin Exp Hematop, 66(1):103-107, 2026.
  3. Inoue Y, Niyama-Uchibori Y, Chinen S, Nakamura T, Okamoto H, Fujino T, Tsukamoto T, Mizutani S, Kuroda J. Multistep molecular trajectory of monocytic myeloid-derived suppressor cell induction by diffuse large B-cell lymphoma cells. Biochem Biophys Res Commun, 804:153287, 2026. 
  4. Makita S, Izutsu K, Mishima Y, Kumode T, Kuroda J, Kanemura N, Fukuhara N, Shimada K, Mori C, Kawasaki A, Miyake T, Maruyama D. Efficacy and safety of subcutaneous mosunetuzumab in combination with lenalidomide and as a monotherapy in Japanese patients with relapsed/refractory follicular lymphoma. Int J Clin Oncol, 31(3):456-466, 2026.
  5. Kato D, Fujino T, Isa R, Okamoto H, Tsukamoto T, Mizutani S, Shimura Y, Kobayashi T, Uchiyama H, Taniwaki M, Miyagawa-Hayashino A, Kuroda J. Immunophenotypically diverse immature patterns, including variable TdT expression, in aggressive B-cell lymphomas and leukemia with MYC rearrangement. Front Oncol, 15:1684005, 2025.
  6. Ohmachi K, Kinoshita T, Maruyama D, Machida R, Sano Y, Yamauchi N, Fukuhara N, Uchida T, Yamamoto K, Miyazaki K, Tsukamoto N, Iida S, Yoshida I, Imaizumi Y, Suzuki Y, Yoshida S, Masaki Y, Murayama T, Yakushijin Y, Suehiro Y, Nosaka K, Dobashi N, Kuroda J, Takamatsu Y, Munakata W, Ando K, Ishizawa K, Ogura M, Yoshino T, Hotta T, Tsukasaki K, Tobinai K, Nagai H. Final results of JCOG0601 randomized trial of R-CHOP versus CHOP combined with dose-dense rituximab for diffuse large B-cell lymphoma. Jpn J Clin Oncol. 55(12):1357-1364, 2025
  7. Miyashita A, Murao T, Shimura Y, Okamoto H, Nagata H, Onishi A, Fujino T, Mizutani S, Tsukamoto T, Kuroda J. Late-Onset Angioimmunoblastic T-cell Lymphoma During Nivolumab Treatment for Melanoma. Cureus 17(7): e89042.
  8. Murao T, Yamane Y, Kiyota M, Shiozaki N, Wada K, Kamitsuji Y, Kuroda J, Kawata E. The Emergence of Subclones Following Initial Chemotherapy in Mixed Phenotype Acute Leukemia. Cureus 17(7): e87163, 2025.
  9. Kitai J, Seno T, Kohno M, Hashimoto K, Mizutani S, Kuroda J, Masaki Y, Kawahito Y. Atypical Lymphoproliferative Disorder and Acquired Angioedema in Systemic Lupus Erythematosus and Sjögren's Syndrome: A Diagnostic Challenge. Mod Rheumatol Case Rep. 9(2):rxaf022, 2025.
  10. Okayama Y, Takakuwa T, Shimura Y, Imada K, Kosugi S, Hotta M, Fuchida SI, Tanaka H, Uoshima N, Yoshihara S, Kanda J, Shibayama H, Fukushima K, Ohta K, Yagi H, Ito T, Shimazaki C, Matsumura I, Takaori-Kondo A, Hosen N, Hino M, Kuroda J. Insights into very elderly multiple myeloma treatment from Kansai Myeloma Forum. Hematology. 30(1):2496545, 2025.
  11. Kim WS, Kim TM, Cho SG, Jarque I, Iskierka-Jażdżewska E, Poon LM, Prince HM, Zhang H, Cao J, Zhang M, Tessoulin B, Oh SY, Lim F, Carpio C, Tan TD, Ayyappan S, Gutierrez A, Cai J, Ufkin M, Shariff S, Brouwer-Visser J, Chaudhry A, Mohamed H, Ambati S, Walewski J; ELM-2 Investigators: Rose H, Chong G, Ganju V, Chu M, Keating MM, Song Y, Zhu J, Ke X, Yi S, Zhang H, Zhang Q, Zou L, Zhang M, Li D, Qian W, Bai O, Gao L, Jin J, Li C, Huang H, Wei Z, Chen Y, He P, Damaj LG, Bouabdballah K, Bachy E, Haioun C, Morschhauser F, Choquet S, Delwail V,  Thieblemont C, Duell J, Weber T, La Rosee PG, Hebart H, Capochiani E, Zilioli V, Rossi F, Luminari S, Zinzani PL, Bagnato L, Gaidano G, Brociner M, Skert C, Tani M, Battistini R, Flenghi L, Yamamoto R, Tsukasaki K, Ishizawa K, Tobai T, Uchida T, Minami Y, Yamauchi N, Yuda J, Takeuchi M, Nagai H, Suehiro Y, Ogawa Y, Kuroda J, Jo T, Nakamae H, Yoshida I, Taszner M, Lech-Maranda E, Knopinska-Posluszny W, Wrobel T,  Robak T, Hsieh WS, Ong SY, Eom HS, Mun YS, Do YR, Kim JS, Kim BS, Jo JC, Jimenez-Ubieto A, Andreu R, Martin A, Coello AP, Cordoba R, Alonso A, Magnano L, Gonzalez-Barca E, Miqueleiz S, Chen TY, Yeh SP, Wu SJ, Wang MC, Cunningham D, Kuhnl A, Tucker D, Lewis D, Elmusharaf N, Allan J, Jandl T, Ibrahimi S, Jagadeesh D, Leslie L, Venugopal P, Arnason J, Villasboas JC, Vaidya R, Stevens D, Awan F, Klein A, Farooq U. Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial. Nat Cancer. 2025, 6(5):907.
  12. Onishi A, Miyagawa-Hayashino A, Okamoto H, Fujino T, Tuskamoto T, Mizutani S, Shimura Y, Konishi E, Kuroda J. Phosphorylation status and prognostic impacts of RSK2, PDPK1, and AKT in malignant lymphoma. Leuk Lymphoma, 66(8):1413-1424,2 2025.
  13. Fujino T, Okamoto H, Nishiyama D, Hayata H, Sasaki N, Kobayashi T, Maekura C, Kuwahara-Ota S, Takimoto-Shimomura T, Shimura K, Kawaji-Kanayama Y, Inoue Y, Chinen S, Isa R, Tsukamoto T, Mizutani S, Shimura Y, Kaneko H, Nakao M, Fuchida S, Takahashi R, Uchiyama H, Uoshima N, Kuroda J, Kyoto Clinical Hematology Study Group. Real-world data of Polatuzumab Vedotin with Bendamustine and Rituximab for Japanese relapsed and refractory DLBCL： A Multicenter Retrospective Study. Leuk Lymphoma, 66(8):1425-1436, 2025.
  14. Fukuhara N, Yoshida I, Ishiguro T, Fujimoto K, Kuroda J, Uchida T, Yamamoto R, Ogawa Y, Hiramatsu Y, Ito T, Katagiri S, Nakazato T, Suzukawa K, Kinami K, Zhou M, Negoro E. PI3Kδ inhibitor parsaclisib in Japanese patients with relapsed or refractory follicular lymphoma. Cancer Sci, 116(8):2189-2197, 2025.
  15. Makishima H, Mikasa T, Isogaya K, Miyamoto T, Yamauchi T, Yokota A, Onozawa M, Ando K, Ogawa Y, Usuki K, Yamauchi T, Ota S, Takada S, Morita Y, Ishikawa T, Takenaka K, Kuroda J, Sekiguchi N, Kawakita T, Miyazaki Y. Association between gene mutations and outcomes in Japanese high-risk AML patients: a phase 1/2 study of NS-87/CPX-351. Int J Hematol. 2025, 122(1):57-65, 2025.
  16. Iyama S, Chi S, Idogawa M, Ikezoe T, Fukushima K, Utsu, Kanda J, Yoshimoto G, Kobayashi T, Hosono N, Yamauchi T, Kondo T, Nakamura Y, Kojima K, Yoshida, Gotoh A, Yamamoto K, Kuroda J, Ishitsuka K, Sakaida E, Horiguchi H, Takada K, Ohnishi H, Kobune M, Minami Y, all HM-SCREEN-Japan 01/02 investigators. Prognostic impact of TET2 mutations in patients with acute myeloid leukemia: HM-SCREEN- Japan 01 and 02 study. Ann Hematol, 104(1):275-284, 2025.
  17. Nagata H, Tsukamoto T, Kobayashi T, Takahashi R, Okano A, Uchiyama H, Kawata E, Uoshima N, Kaneko H, Fuchida S, Nishiyama D, Nakao M, Fujino T, Mizutani S, Shimura Y, Kuroda J. The real-world efficacy and safety of frontline therapy of obinutuzumab plus bendamustine for untreated high-tumor-burden follicular lymphoma. Int J Clin Oncol, 30(3):593-603, 2025.
  18. Ri M, Iida S, Saito K, Saito Y, Maruyama D, Asano A, Fukuhara S, Tsujimura H, Miyazaki K, Ota S, Fukuhara N, Negoro E, Kuroda J, Yoshida S, Otsuka E, Tsukamoto N, Tabayashi T, Takayama N, Saito T, Suzuki Y, Harada Y, Mizuno I, Yoshida I, Maruta M, Takamatsu Y, Katsuya H, Yoshimitsu M, Minami Y, Kanato K, Munakata W, Nagai H. Lipidomic profiling of plasma from patients with multiple myeloma receiving bortezomib: An exploratory biomarker study of JCOG1105. Cancer Chemother Pharmacol, 95(1): 29, 2025.
  19. Inoue Y, Tsukamoto T, Mizuhara K, Maekura C, Nakamura T, Okamoto H, Fujino T, Mizutani S, Shimura S, Maruyama A, Nakanishi M, Tanaka F, Nishida Y, Ishii K, Sonobe Y, Miyagawa-Hayashino A, Kuroda J. Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma complicated by paraneoplastic encephalitis. Intern Med, 64(17):2641-2645, 2025.
  20. Okamoto H, Mizutani S, Tsukamoto T, Katsuragawa-Taminishi Y, Kawaji-Kanayama Y, Mizuhara K, Muramatsu A, Isa R, Fujino T, Shimura Y, Ichikawa K, Kuroda J. Robust Anti-myeloma Effect of TAS0612, an RSK/AKT/S6K Inhibitor, with Venetoclax Regardless of Cytogenetic Abnormalities. Leukemia 39(1): 211-221, 2025.
  21. Izutsu K, Ando K, Nishikori M, Shibayama H, Goto H, Kuroda J, Kato K, Imaizumi Y, Nosaka K, Sakai R, Abe M, Hojo S, Nakanishi T, Rai S. Tazemetostat for relapsed/refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan: 3-year follow-up for a phase II study. Int J Hematol 120(5); 621-630, 2024.
  22. Shimazu Y, Kanda J, Takakuwa T, Onda Y, Fukushima K, Hotta M, Fuchida S, Uoshima N, Shimura Y, tanaka K, Ohta K, Shibayama H, Kosugi S, Yagi H, Yoshihara S, Hosen N, Ito T, Shimazaki C, Matsumura I, Kuroda J, Takaori-Kondo A, Hino M. The Impact of renal function on initial therapy in transplant-ineligible multiple myeloma patients. Ann Hematol 103(12); 5639-5649, 2024.
  23. Niiyama-Uchibori Y, Mizutani S, Tsukamoto T, Okamoto H, Ide D, Onishi A, Kato D, Fujino T, Shimira Y, Miyagawa-Hayashino A, Konishi E, Karube K, Nannya Y, Kuroda J. Small cell pattern of ALK-negative anaplastic large cell lymphoma with double hit rearrangements of DUSP22 and TP63. eJHaem 5(4): 798-801, 2024.
  24. Shishido-Hara Y, Miyagawa-Hayashino A, Kuroda J. B-cell maturation in angioimmunoblastic T cell lymphoma (AITL): Development of secondary diffuse large B cell lymphoma (DLBCL) is likely associated with Attygalle patterns II and III. Medical Research Archives 12(9), 2024.
  25. Shishido-Hara Y, Iguchi R, Kuroda J. An autopsy case of EBV-positive CD8+ T cell lymphoma after allogeneic transplantation of peripheral blood stem cells. Medical Research Archives 12(9), 2024.
  26. Harada Y, Makino M, Nakao R, Shimura Y, Ogata T, Hayakawa M, Shiraishi H, Kuroda J, Matoba S, Tanaka H. An Autopsy Case of Severe COVID-19 Pneumonia Complicated by Intrapulmonary Thrombosis in Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis. Cureus 16(6): e62790, 2024.
  27. Rai S, Kim WS, Ando K, Choi I, Izutsu K, Tsukamoto N, Maruyama D, Tsukasaki K, Kuroda J, Ando J, Hidaka M, Koh Y, Kato H, Uchida T, Yang DH, Ishitsuka K, Ishizawa K, Kim JS, Lee HG, Minami H, Eom HS, Kurosawa M, Lee JH, Lee JS, Lee WS, Nagai H, Shindo T, Yoon DH, Yoshida S, Gillings M, Onogi H, Tobinai K. Long-term efficacy and safety of tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: Final analysis of phase IIb results. Haematologica, 109(10): 3357-3362, 2024.
  28. Shimazu Y, Kanda J, Onda Y, Fuchida SI, Ohta K, Shimura Y, Kosugi S, Yamamura R, Matsuda M, Hanamoto H, Adachi Y, Anzai N, Hotta M, Fukushima K, Yagi H, Yoshihara S, Tanaka Y, Takakuwa T, Tanaka H, Shibayama H, Uoshima N, Hosen N, Ito T, Shimazaki C, Matsumura I, Kuroda J, Takaori-Kondo A, Hino M. The lymphocyte/monocyte ratio predicts the efficacy of isatuximab plus pomalidomide in multiple myeloma patients. Cancer Immunol Immunother. 73:135, 2024.
  29. Hashiro W, Miyashita A, Kawaji-Kanayama Y, Okamoto H, Fujino T, Tsukamoto T, Mizutani S,  Shimura Y, Kuroda J. Good’s Syndrome With Pure Red Cell Aplasia and Subclinical Myasthenia Gravis: A Case Report and Review of Literature. Cureus, 16（5）：e59654, 2024. 
  30. Yamamoto C, Taniguchi M, Furukawa K, Inaba T, Niiyama Y, Ide D, Mizutani S, Kuroda J, Tanino Y, Nishioka K, Watanabe Y, Takayama K, Nakaya T, Nukui Y. Nirmatrelvir Resistance in an Immunocompromised Patient with Persistent Coronavirus Disease 2019. Viruses, 16(5):718, 2024.
  31. Shibayama H, Itagaki M, Handa H, Yokoyama A, Saito A, Kosugi S, Ota S, Yoshimitsu M, Tanaka Y, Kurahashi S, Fuchida SI, Iino M, Shimizu T, Moriuchi Y, Toyama K, Mitani K, Tsukune Y, Kada A, Tamura H, Abe M, Iwasaki H, Kuroda J, Takamatsu H, Sunami K, Kizaki M, Ishida T, Saito T, Matsumura I, Akashi K, Iida S. Primary analysis of a prospective cohort study of Japanese patients with plasma cell neoplasms in the novel drug era (2016-2021). Int J Hematol. 119: 707-721, 2024.
  32. Watanabe T, Matsuno Y, Wakabayashi M, Maruyama D, Yamamoto K, Kubota N, Shimada K, Asagoe K, Yamaguchi M, Ando K, Ogura M, Kuroda J, Suehiro Y, Tsukasaki K, Tobinai K, Nagai H. Analyzing the risk factors for disease progression within 2 years and histological transformation in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as first-line treatment: A 15-year follow-up of patients with advanced follicular lymphoma in JCOG0203. Hematol Oncol, 42: e3272, 2024.
  33. Mori Y, Takizawa J, Katsuoka Y, Takezako N, Nagafuji K, Handa H, Kuroda J, Sunami K, Kamimura T, Ogawa R, Kikushige Y, Harada M, Akashi K, Miyamoto,T. Autologous HSCT with Novel Agent-Based Induction Followed by Lenalidomide Maintenance for Untreated Multiple Myeloma. Cancer Sci, 115: 2002-2011, 2024.
  34. Nakamura N, Arima N, Takakuwa T, Yoshioka S, Imada K, Fukushima K, Hotta M, Fuchida S, Kanda J, Uoshima N, Shimura Y, Tanaka H, Ohta K, Kosugi S, Yagi H, Yoshihara S, Yamamura R, Adachi Y, Hanamoto H, Shibayama H, Hosen N, Ito T, Shimazaki C, Takaori-Kondo A, Kuroda J, Matsumura I, Hino M. Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study. Ann Hematol, 103: 5681-5690, 2024.
  35. Kogure Y, Handa H, Ito Y, Ri M, Horigome Y, Iino M, Harazaki Y, Kobayashi T, Abe M, Ishida T, Ito S, Iwasaki H, Kuroda J, Shibayama H, Sunami K, Takamatsu H, Tamura H, Hayashi T, Akagi K, Shinozaki T, Yoshida T, Mori I, Iida S, Maeda T, Kataoka K. ctDNA improves prognostic prediction in relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone. Blood, 143: 2401-2413, 2024.
  36. Ide D, Fujino T, Kobayashi T, Egashira A, Miyashita A, Mizuhara K, Isa R, Tsukamoto T, Mizutani S, Uchiyama H, Kaneko H, Uoshima N, Kawata E, Taniwaki M, Shimura Y, Kuroda J, and Kyoto Clinical Hematology Study Group. Prognostic model for relapsed/refractory transplant-ineligible diffuse large B cell lymphoma utilizing the lymphocyte-to-monocyte ratio. Int J Hematol, 119: 697-706, 2024.
  37. Niiyama-Uchibori Y, Okamoto H, Miyashita A, Mizuhara K, Kanayama-Kawaji Y, Fujino T, Tsukamoto T,  Mizutani S, Shimura Y, Teramukai S, Kuroda K. Skeletal muscle index impacts the treatment outcome of elderly patients with diffuse large B cell lymphoma. Hematol Oncol, 42:e3252, 2024.
  38. Watanabe T, Tobinai K, Wakabayashi M, Maruyama D, Yamamoto K, Kubota N, Shimada K, Asagoe K, Yamaguchi M, Ando K, Ogura M, Kuroda J, Suehiro Y, Matsuno Y, Tsukasaki K, Nagai H. Long-Term Safety and Efficacy of Advanced Follicular Lymphoma Patients Treated With Front-Line R-CHOP. Br J Haematol, 204: 849-860, 2024.
  39. Kawaji-Kanayama Y, Tsukamoto T, Nakano M, Tokuda Y, Nagata H, Mizuhara K, Katsuragawa-Taminishi Y, Isa R, Fujino T, Matsumura-Kimoto Y, Mizutani S, Shimura Y, Taniwaki M, Tashiro K, Kuroda J. miR-17-92 cluster-BTG2 axis regulates B-cell receptor signaling in mantle cell lymphoma. Cancer Sci, 115:452-464, 2024.
  40. Onishi A, Matsumura-Kimoto Y, Mizutani S, Isa R, Fujino T, Tsukamoto T, Miyashita A, Okumura K, Nishiyama D, Hirakawa K, Shimura K, Kaneko H, Kiyota M, Kawata E, Takahashi R, Kobayashi T, Uchiyama H, Uoshima N, Nukui Y, Shimura Y, Inaba T, Kuroda J, Kyoto Clinical Hematology Study Group investigators. Negative impact of immunoparesis in the response to anti-SARS-CoV-2 mRNA vaccination of patients with multiple myeloma. Int J Hematol, 119: 50-61, 2024.
  41. Horigome Y, Iino M, Harazaki Y, Kobayashi T, Handa H, Hiramatsu Y, Kuroi T, Tanimoto K, Matsue K, Abe M, Ishida T, Ito S, Iwasaki H, Kuroda J, Shibayama H, Sunami K, Takamatsu H, Tamura H, Hayashi T, Akagi K, Maeda T, Yoshida T, Mori I, Shinozaki T, Iida S. A prospective, multicenter, observational study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in Japan. Ann Hematol, 103; 475-488, 2024.
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