Characterization molecular and immunologic features of CML stem cells for treatment-free remission.
Project/Area Number |
18K08375
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Kindai University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
田中 宏和 近畿大学, 医学部, 准教授 (40360846)
頼 晋也 近畿大学, 医学部, 講師 (70460855)
森田 泰慶 近畿大学, 医学部, 講師 (80411594)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 慢性骨髄性白血病 / 分子標的 / 腫瘍免疫 / アミノ酸代謝 / CML / CML幹細胞 / チロシンキナーゼ阻害薬 / 免疫チェックポイント分子 |
Outline of Final Research Achievements |
In this study, we analyzed immune evasion mechanisms of residual chronic myeloid leukemia stem cells (CML-LSCs) during the treatment with tyrosine kinase inhibitors (TKIs). Both expression of immune checkpoint molecule, PDL1 and activation of immunosuppressive enzyme, IDO1 were induced through the activation of CD120a/NF-κB signaling pathway in phenotypically defined CD34+38-120a+225+ cells, which we previously identified as CML-LSC. Furthermore, CML-LSCs suppressed cytotoxic T cell activity and induced a local recruitment of immunosuppressive populations such as regulatory T cells and myeloid-derived suppressor cells, leading to an immunosuppressive bone marrow milieu undergoing TKI therapy.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、CMLの免疫回避機構における腫瘍免疫とアミノ酸代謝との関連を明らかにしたものであり学術的意義は高い。本研究により、組織内IDO1活性を指標としたTKI の中止可能な症例の選別法だけでなく、治癒に向けたIDO1阻害によるCML-LSCに対する新規治療法を開発する上で、重要な知見が得られたと考えられる。
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] Combination of clofarabine, etoposide, and cyclophosphamide in adult relapsed/refractory acute lymphoblastic leukemia: a phase 1/2 dose-escalation study by the Japan Adult Leukemia Study Group.2021
Author(s)
Saito T, Hatta Y, Hayakawa F, Takahashi T, Hagihara M, Iida H, Minauchi K, Yamazaki E, Sugiura I, Murayama T, Sakura T, Mori N, Imai K, Yahagi Y, Atsuta Y, Saito AM, Hirakawa A, Kiyoi H, Matsumura I, Miyazaki Y
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Journal Title
Int J Hematol.
Volume: 113
Issue: 3
Pages: 395-403
DOI
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Peer Reviewed / Open Access
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[Journal Article] The Impact of Hemodialysis and Liver Cirrhosis on the Plasma Concentrations of Tyrosine Kinase Inhibitors in a Patient with Chronic Myeloid Leukemia2020
Author(s)
Taniguchi Y, Takahashi N, Miura M, Hirase C, Sueda S, Espinoza JL, Rai S, Nakayama S, Serizawa K, Kumode T, Watatani Y, Morita Y, Tanaka H, Matsumura I.
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Journal Title
Internal Medicine
Volume: 59
Issue: 21
Pages: 2745-2749
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2020-11-01
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Peer Reviewed / Open Access
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[Journal Article] Impact of CD56 Continuously Recognizable as Prognostic Value of Acute Promyelocytic Leukemia: Results of Multivariate Analyses in the Japan Adult Leukemia Study Group (JALSG)-APL204 Study and a Review of the Literature.2020
Author(s)
Takeshita A, Asou N, Atsuta Y, Furumaki H, Sakura T, Ueda Y, Sawa M, Dobashi N, Taniguchi Y, Suzuki R, Nakagawa M, Tamaki S, Hagihara M, Fujimaki K, Minamiguchi H, Fujita H, Yanada M, Maeda Y, Usui N, Kobayashi Y, Kiyoi H, Ohtake S, Matsumura I, Naoe T, Miyazaki Y.
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Journal Title
Cancers (Basel)
Volume: 12(6)
Issue: 6
Pages: 1444-1444
DOI
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Peer Reviewed / Open Access
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[Journal Article] Treatment outcomes of chronic-phase chronic myeloid leukemia with resistance and/or intolerance to a 1st-line tyrosine kinase inhibitor in Japan: the results of the New TARGET study 2nd-line2020
Author(s)
Sakurai M, Okamoto S, Matsumura I, Murakami S, Takizawa M, Waki M, Hirano D, Watanabe-Nakaseko R, Kobayashi N, Iino M, Mitsui H, Ishikawa Y, Takahashi N, Kawaguchi T, Suzuki R, Yamamoto K, Kizaki M, Ohnishi K, Naoe T, Akashi K; New TARGET investigators.
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Journal Title
Int J Hematol.
Volume: 111
Issue: 6
Pages: 912-825
DOI
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[Journal Article] Phase 2 study of bosutinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia.2020
Author(s)
Hino M, Matsumura I, Fujisawa S, Ishizawa K, Ono T, Sakaida E, Sekiguchi N, Tanetsugu Y, Fukuhara K, Ohkura M, Koide Y, Takahashi N.
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Journal Title
International Journal of Hematology
Volume: Epub ahead of print
Issue: 1
Pages: 24-32
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chlorpromazine eliminates acute myeloid leukemia cells by perturbing subcellular localization of FLT3-ITD and KIT-D816V.2020
Author(s)
Shinya Rai, Hirokazu Tanaka*, Mai Suzuki, J. Luis Espinoza, Takahiro Kumode, Akira Tanimura, Yasuyoshi Morita, Yoichi Tatsumi, Takafumi Yokota, Kenji Oritani, Toshio Watanabe, Yuzuru Kanakura, and Itaru Matsumura.
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Journal Title
Nature Communications
Volume: 11
Issue: 1
Pages: 4147-4147
DOI
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Peer Reviewed / Open Access
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[Journal Article] Tamibarotene maintenance improved relapse-free survival of acute promyelocytic leukemia: a final result of prospective, randomized, JALSG-APL204 study.2019
Author(s)
Takeshita A, Asou N, Atsuta Y, Sakura T, Ueda Y, Sawa M, Dobashi N, Taniguchi Y, Suzuki R, Nakagawa M, Tamaki S, Hagihara M, Fujimaki K, Furumaki H, Obata Y, Fujita H, Yanada M, Maeda Y, Usui N, Kobayashi Y, Kiyoi H, Ohtake S, Matsumura I, Naoe T, Miyazaki Y
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Journal Title
Leukemia
Volume: 33
Issue: 2
Pages: 358-370
DOI
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[Journal Article] Efficacy and safety of tyrosine kinase inhibitors for newly diagnosed chronic-phase chronic myeloid leukemia over a 5-year period: results from the Japanese registry obtained by the New TARGET system.2019
Author(s)
Kizaki M, Takahashi N, Iriyama N, Okamoto S, Ono T, Usui N, Inokuchi K, Nakaseko C, Kurokawa M, Sumi M, Nakamura F, Kawaguchi T, Suzuki R, Yamamoto K, Ohnishi K, Matsumura I, Naoe T; New TARGET investigators.
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Journal Title
Int J Hematol
Volume: 109
Issue: 4
Pages: 426-439
DOI
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Peer Reviewed / Open Access
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[Journal Article] Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years: a multicenter phase 2 trial, stop nilotinib (NILSt).2019
Author(s)
Nagafuji K, Matsumura I, Shimose T, Kawaguchi T, Kuroda J, Nakamae H, Miyamoto T, Kadowaki N, Ishikawa J, Imamura Y, Yamazaki H, Akashi K, Kanakura Y.
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Journal Title
Int J Hematol
Volume: 110
Issue: 6
Pages: 675-682
DOI
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Peer Reviewed / Open Access
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[Journal Article] Classic Hodgkin Lymphoproliferative Diseases Clonally Unrelated to B-Chronic Lymphocytic Leukemia Successfully Treated with Bendamustine Plus Rituximab.2018
Author(s)
Rai S, Tanaka H, Fujimoto K, Kumode T, Inoue H, Taniguchi Y, Morita Y, Espinoza JL, Tatsumi Y, Ashida T, Matsuoka R, Kikuti YY, Nakamura N, Matsumura I.
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Journal Title
Cancers (Basel).
Volume: 10
Issue: 9
Pages: 304-304
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Retrospective analysis of primary plasma cell leukemia in Kansai Myeloma Forum registry2018
Author(s)
Nakaya A, Yagi H, Kaneko H, Kosugi S, Kida T, Adachi Y, Shibayama H, Kohara T, Kamitsuji Y, Fuchida SI, Uoshima N, Kawata E, Uchiyama H, Shimura Y, Takahashi T, Urase F, Ohta K, Hamada T, Miyamoto K, Kobayashi M, Shindo M, Tanaka H, Shimazaki C, Hino M, Kuroda J, Kanakura Y, Takaoari-Kondo A, Nomura S, Matsumura I
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Journal Title
Leukemia Research Reports
Volume: 10
Pages: 7-10
DOI
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[Journal Article] Infectious complications in adults undergoing intensive chemotherapy for acute myeloid leukemia in 2001-2005 using the Japan Adult Leukemia Study Group AML201 protocols.2018
Author(s)
Kato H, Fujita H, Akiyama N, Kimura SI, Hiramoto N, Hosono N, Takahashi T, Shigeno K, Minamiguchi H, Miyatake J, Handa H, Kanda Y, Yoshida M, Miyawaki S, Ohtake S, Naoe T, Kiyoi H, Matsumura I, Miyazaki Y
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Journal Title
Support Care Cancer
Volume: 26
Issue: 12
Pages: 4187-4198
DOI
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[Journal Article] Pomalidomide with or without dexamethasone for relapsed/refractory multiple myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum2018
Author(s)
Matsumura-Kimoto Y, Kuroda J, Kaneko H, Kamitsuji Y, Fuchida SI, Nakaya A, Shibayama H, Uoshima N, Yokota I, Uchiyama H, Yagi H, Kosugi S, Matsui T, Ishikawa J, Matsuda M, Ohta K, Iida M, Tanaka H, Kobayashi M, Wada K, Shimazaki C, Nomura S, Imada K, Hino M, Matsumura I, Kanakura Y, Takaori-Kondo A; KMF
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Journal Title
International Journal of Hematology
Volume: 107
Issue: 5
Pages: 541-550
DOI
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[Journal Article] Nilotinib vs. imatinib in Japanese patients with newly diagnosed chronic myeloid leukemia in chronic phase: long-term follow-up of the Japanese subgroup of the randomized ENESTnd trial2017
Author(s)
Nakamae H, Fukuda T, Nakaseko C, Kanda Y, Ohmine K, Ono T, Matsumura I,Matsuda A, Aoki M, Ito K, Shibayama H.
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Journal Title
Int J Hematol.
Volume: 107
Issue: 3
Pages: 327-336
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[Presentation] 症候性骨髄腫1414例の後方視的解析:関西骨髄腫フォーラムからの最新報告2018
Author(s)
田中 宏和, 芹澤 憲太郎, 中谷 綾, 金子 仁臣, 太田 健介, 小杉 智, 八木 秀男, 花本 仁, 淵田 真一, 志村 勇司, 柴山 浩彦, 小原 尚恵, 中谷 英仁, 諫田 淳也, 魚嶋 伸彦, 和田 勝也, 烏野 隆博, 松井 利充, 内山 人二, 松田 光弘, 足立 陽子, 高折 晃史, 黒田 純也, 谷脇 雅史, 島崎 千尋, 日野 雅之, 今田 和典, 野村 昌作, 金倉 譲, 松村 到
Organizer
第80回日本血液学会学術集会
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[Presentation] CD34陽性ヒト骨髄腫幹細胞の同定と特性解析2018
Author(s)
芹澤 憲太郎, 田中 宏和, 福井 彩乃, 藤原 亮介, 佐野 圭吾, 口分田 貴裕, 谷口 康博, 森田 泰慶, ルイス エスピノザ, 辰巳 陽一, 芦田 隆司, 松村 到
Organizer
第80回日本血液学会学術集会
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[Presentation] 異常なRTKの細胞内輸送阻害は急性骨髄性白血病における有望な治療標的である。2018
Author(s)
頼 晋也 田中 宏和, 鈴木 麻衣, Luis Espinoza, 谷村 朗, 森田 泰慶, 辰巳 陽一, 横田 貴史, 織谷 健司, 渡邊 俊雄, 金倉 譲, 松村 到
Organizer
第80回日本血液学会学術集会
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