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。

 

2. 多発性骨髄腫の分子生物学・細胞遺伝学的多様性の克服戦略開発

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。

 

3. 造血器腫瘍における腫瘍免疫監視機構再教育の戦略開発

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

 

4. 腫瘍環境による造血器腫瘍の病態形成支持機序の解明と治療標的化

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。

 

5. 造血器疾患治療における治療法・合併症管理・支持療法向上のための臨床研究

 

Tsukamoto T, Kinoshita M, Yamada K, Ito H, Yamaguchi T, Chinen Y, Mizutani S, Fujino T, Kobayashi T, Shimura Y, Inazawa J, Kuroda J. Imaging flow cytometry-based multiplex FISH for three IGH translocations in multiple myeloma. J Hum Genet, in print.

 

Onishi A, Matsumura-Kimoto Y, Mizutani S, Tsukamoto T, Fujino T, Miyashita A, Nishiyama D, Shimura K, Kaneko H, Kawata E, Takahashi R, Kobayashi T, Uchiyama H, Uoshima N, Nukui Y, Shimura Y, Inaba T, Kuroda J. Impact of treatment with anti-CD20 monoclonal antibody on the production of neutralizing antibody against anti–SARS-CoV-2 vaccination in mature B-cell neoplasms. Infect Drug Resist, 16, 509-519, 2023.

 

Mizuhara K, Kobayashi T, Nakao M, Takahashi R, Kaneko H, Shimura K, Hirakawa K, Uoshima N, Wada K, Kawata E, Isa R, Fujino T, Tsukamoto T, Mizutani S, Shimura Y, Yoneda A, Watanabe A, Sotozono C, Kuroda J. Watchful waiting is an acceptable treatment option for asymptomatic primary ocular adnexal mucosa-associated lymphoid tissue lymphoma: a retrospective study. Cancer Med, 12, 3134-3144, 2023.

 

Maekura C, Muramatsu A, Nagata H, Okamoto H, Onishi A, Kato D, Isa R, Fujino T, Tsukamoto T, Mizutani S, Shimura Y, Kobayashi T, Okumura K, Inaba T, Nukui Y, Kuroda J.. Clinical implication of the effect of the production of neutralizing antibodies against SARS-Cov-2 for chronic immune thrombocytopenia flare-up associated with COVID-19 infection; a case report and the review of literature. Infect Drug Resist, 15, 2723-2728, 2022.

 

Isa R, Horinaka M, Tsukamoto T, Mizuhara K, Fujibayashi Y, Taminishi-Katsuragawa Y, Okamoto H, Yasuda S, Kawaji-Kanayama Y, Matsumura-Kimoto Y, Mizutani S, Shimura Y, Taniwaki M, Sakai T, Kuroda J. The rationale for the dual targeting therapy for RSK2 and AKT in multiple myeloma. Int J Mol Sci, 23, 2919, 2022.

 

Kobayashi T, Yamamoto K, Kagami Y, Machida R, Miyazaki K, Nakamura S, Kuroda J, Maruyama D, Nagai H. Prognostic value of the Kyoto Prognostic Index in higher-risk diffuse large B-cell lymphomas treated by upfront autologous stem cell transplantation in JCOG0908 trial. Jpn J Clin Oncol, 52, 583-588, 2022.

 

Fujino T, Maruyama D, Miyagi-Maeshima A, Tajima K, Saito Y, Ida H, Hosoba R, Yuda S, Makita S, Fukuhara S, Munakata W, Suzuki T, Kuroda J, Izutsu K. The outcome of watchful waiting in patients with previously treated follicular lymphoma. Cancer Med, 11, 2106-2116, 2022.

 

Muramatsu A, Kobayashi T, Kawaji-Kanayama Y, Uchiyama H, Sasaki N, Uoshima N, Nakao M, Takahashi R, Shimura K, Kaneko H, Kiyota M, Wada K, Chinen Y, Hirakawa K, Fuchida S, Shimazaki C, Mizutani S, Tsukamoto T, Shimura Y, Taniwaki M, Teramukai S, Kuroda J, Kyoto Clinical Hematology Study Group (KOTOSG) Investigators. Pretreatment serum level of interleukin-6 predicts carfilzomib-induced hypertension in relapsed/refractory multiple myeloma. Leuk Lymphoma, 11, 1-8, 2022.

 

Tsukamoto T, Tokuda Y, Nakano M, Tashiro K, Kuroda J. Expression of activated B cell gene signature is predictive of the outcome of follicular lymphoma. Blood Adv, 6, 1932-1936, 2022.

 

Kawaji-Kanayama Y, Muramatsu A, Sasaki N, Shimura K, Kiyota M, Fuchida S, Isa R, Fujino T, Matsumura-Kimoto Y, Tsukamoto T, Chinen Y, Mizutani S, Nakao M, Kaneko H, Kawata E, Hirakawa K, Takahashi R, Shimazaki C, Uchiyama H, Uoshima N, Shimura Y, Kobayashi T, Taniwaki M, Kuroda J, Kyoto Clinical Hematology Study Group (KOTOSG) Investigators. Clinical impacts of frailty, poor performance status, and advanced age in carfilzomib-containing treatment for relapsed/refractory multiple myeloma: post hoc investigation of the KOTOSG multicenter pilot prospective observational study. Int J Hematol, 115, 350-362, 2022.

 

Okamoto H, Uoshima N, Muramatsu A, Isa R, Fujino T, Matsumura-Kimoto Y, Tsukamoto T, Mizutani S, Shimura Y, Kobayashi T, Kawata E, Uchiyama H, Kuroda J, Kyoto Clinical Hematology Study Group investigators* Combination of bone marrow biopsy and flow cytometric analysis: The prognostically relevant central approach for detecting bone marrow invasion in diffuse large B-cell lymphoma. Diagnostics, 11:1724, 2021.

 

Kawaji-Kanayama Y, Kobayashi T, Muramatsu A, Uchiyama H, Sasaki N, Uoshima N, Nakao M, Takahashi R, Shimura K, Kaneko H, Kiyota M, Wada K, Chinen Y, Hirakawa K, Fuchida S, Shimazaki C, Matsumura-Kimoto Y, Mizutani S, Tsukamoto T, Shimura Y, Horiike S, Taniwaki M, Kuroda J, Kyoto Clinical Hematology Study Group (KOTOSG) Investigators. Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients. Cancer Reports, e1476, 2021.

 

Fujibayashi Y, Isa R, Nishiyama D, Sakamoto-Inada N, Kawasumi N, Yamaguchi J, Kuwahara-Ota S, Matsumura-Kimoto Y, Tsukamoto T, Chinen Y, Shimura Y, Kobayashi T, Horiike S, Taniwaki M, Handa H, Kuroda J. Aberrant BUB1 overexpression promotes mitotic segregation errors and chromosomal instability in multiple myeloma. Cancers, 12: 2206, 2020.

 

Kuwahara-Ota S, Shimura Y, Steinebach C, Isa R, Yamaguchi J, Nishiyama D, Fujibayashi Y, Takimoto-Shimomura T, Mizuno Y, Matsumura-Kimoto Y, Tsukamoto T, Chinen Y, Kobayashi T, Horiike S, Taniwaki M, Gutschow M, Kuroda J. Lenalidomide and pomalidomide potently interfere with induction of myeloid-derived suppressor cells in multiple myeloma. Br J Haematol, 191: 784-795, 2020.