Molecular pathologic elucidation to become usefulness and the choice grounds of the novel FLT3 inhibitor

• Project/Area Number: 17K09921
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Nagoya University
• Principal Investigator: Kiyoi Hitoshi 名古屋大学, 医学系研究科, 教授 (90314004)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 急性骨髄性白血病 / FLT3 / 分子標的薬 / 耐性 / 阻害剤 / 分子標的療法 / 耐性機構 / 分子標的治療 / 血液内科

Outline of Final Research Achievements

We established several PDX models from FLT3 mutation-positive AML cells. Using these PDX models, we analyzed the molecular pathology of AML cells remaining after treatment with quizartinib and gilteritinib, and revealed that AML clones, which express high wild type FLT3 molecules in addition to mutant FLT3 molecules, selectively remained. When the growth inhibitory activities of clinical samples with different expression levels of normal FLT3 molecules were compared, the inhibitory effect was associated with the expression level of normal FLT3 molecules.
We created a model for FLT3 inhibitor resistance in 32D cells transfected with various mutant FLT3s, and identified several novel mutations in the FLT3 kinase domain and the existence of cross-resistance to other FLT3 inhibitors.

Academic Significance and Societal Importance of the Research Achievements

現在、複数のFLT3阻害剤が実用化あるいは臨床開発されている中で、個々のFLT3阻害剤の治療効果を最大限に活用するための薬剤選択・治療アルゴリズムの構築が求められている。
本研究では、白血病細胞における正常FLT3分子の発現量が阻害剤の抗腫瘍効果に相関すると共に、リガンド依存性の正常FLT3分子の活性化に対する阻害剤の感受性によっても治療効果が規定されることを明らかにした。この成果は、実臨床において、阻害薬の特性を見極め、白血病細胞の分子特性を考慮することによって阻害薬の治療効果を高めることにつながる有意義なものである。

Research Products

• [Journal Article] Successful Introduction of Peritoneal Dialysis in an End-stage Renal Failure Patient with Idiopathic Aplastic Anemia (2020)
  • Author(s): Suzuki Yasuhiro、Mizuno Masashi、Sakata Fumiko、Kojima Hiroshi、Sato Yuka、Kishimoto Mayuko、Suzuki Nobuaki、Kinashi Hiroshi、Saito Shoji、Katsuno Takayuki、Kosugi Tomoki、Maruyama Shoichi、Murata Makoto、Kiyoi Hitoshi、Ito Yasuhiko
  • Journal Title: Internal Medicine Volume: 59 Issue: 5 Pages: 683-687
  • DOI: 10.2169/internalmedicine.3775-19
  • NAID: 130007804622
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2020-03-01
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] JSH Practical Guidelines for Hematological Malignancies, 2018: I. Leukemia-1. Acute myeloid leukemia (AML). (2020)
  • Author(s): Kiyoi H, Yamaguchi H, Maeda Y, Yamauchi T
  • Journal Title: Int J Hematol Volume: 111 Issue: 5 Pages: 595-613
  • DOI: 10.1007/s12185-020-02856-3
  • Peer Reviewed
• [Journal Article] Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): a multicentre, single-arm, phase 2 trial (2020)
  • Author(s): Shimada K, Yamaguchi M, Atsuta Y, Kiyoi H, Suzuki R, Tokunaga T, Nakamura S, Kinoshita T
  • Journal Title: The Lancet Oncology Volume: 21 Issue: 4 Pages: 593-602
  • DOI: 10.1016/s1470-2045(20)30059-0
  • Peer Reviewed
• [Journal Article] Higher FVIII:C Measured by Chromogenic Substrate Assay Than by One-Stage Assay Is Associated With Silent Hemophilic Arthropathy (2020)
  • Author(s): Mika Ogawa, Nobuaki Suzuki, Nobunori Takahashi, Shogo Tamura, Atsuo Suzuki, Sachiko Suzuki, Yuua Hattori, Misaki Kakihara, Takeshi Kanematsu, Toshihisa Kojima, Akira Katsumi, Fumihiko Hayakawa, Tetsuhito Kojima, Naoki Ishiguro , Hitoshi Kiyoi , Tadashi Matsushita
  • Journal Title: Thromb Res Volume: 188 Pages: 103-105
  • DOI: 10.1016/j.thromres.2020.01.003
  • NAID: 120006872431
  • Peer Reviewed / Open Access
• [Journal Article] Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study (2020)
  • Author(s): Okada Norio、Iwama Shintaro、Kiyoi Hitoshi、Gotoh Momokazu、Ando Yuichi、Akiyama Masashi、Hasegawa Yoshinori、Arima Hiroshi
  • Journal Title: British Journal of Cancer Volume: 122 Issue: 6 Pages: 771-777
  • DOI: 10.1038/s41416-020-0736-7
  • Peer Reviewed
• [Journal Article] Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia (2020)
  • Author(s): Kiyoi Hitoshi、Morris Joan D、Oh Iekuni、Maeda Yoshinobu、Minami Hironobu、Miyamoto Toshihiro、Sakura Toru、Iida Hiroatsu、Tuglus Catherine A、Chen Yuqi、Dos Santos Cedric、Kalabus James、Anderson Abraham、Hata Tomoko、Nakashima Yasuhiro、Kobayashi Yukio
  • Journal Title: Cancer Science Volume: 111 Issue: 4 Pages: 1314-1323
  • DOI: 10.1111/cas.14322
  • Peer Reviewed / Open Access
• [Journal Article] Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11 (2020)
  • Author(s): Ishikawa Y、Kawashima N、Atsuta Y、Sugiura I、Sawa M、Dobashi N、Yokoyama H、Doki N、Tomita A、Kiguchi T、Koh S、Kanamori H、Iriyama N、Kohno A、Moriuchi Y、Asada N、Hirano D、Togitani K、Sakura T、Hagihara M、Tomikawa T、Yokoyama Y、Asou N、Ohtake S、Matsumura I、Miyazaki Y、Naoe T、Kiyoi H
  • Journal Title: Blood Advances Volume: 4 Issue: 1 Pages: 66-75
  • DOI: 10.1182/bloodadvances.2019000709
  • Peer Reviewed / Open Access
• [Journal Article] FLT3 mutations in acute myeloid leukemia: Therapeutic paradigm beyond inhibitor development (2019)
  • Author(s): Kiyoi Hitoshi、Kawashima Naomi、Ishikawa Yuichi
  • Journal Title: Cancer Science Volume: 111 Issue: 2 Pages: 312-322
  • DOI: 10.1111/cas.14274
  • Peer Reviewed / Open Access
• [Journal Article] Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors (2019)
  • Author(s): Okamoto Shuichi、Suzuki Nobuaki、Suzuki Atsuo、Suzuki Sachiko、Tamura Shogo、Suzuki Mochihito、Takahashi Nobunori、Kojima Toshihisa、Kanematsu Takeshi、Kojima Tetsuhito、Kiyoi Hitoshi、Ishiguro Naoki、Matsushita Tadashi
  • Journal Title: TH Open Volume: 03 Issue: 04 Pages: e364-e366
  • DOI: 10.1055/s-0039-3401001
  • Peer Reviewed / Open Access
• [Journal Article] ZNF384-fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities. (2019)
  • Author(s): 3.Yamamoto H, Hayakawa F, Yasuda T, Odaira K, Minamikawa Y, Tange N, Hirano D,Kojima Y, Morishita T, Tsuzuki S, Naoe T, Kiyoi H.
  • Journal Title: FEBS Lett. Volume: 593 Issue: 16 Pages: 2151-2161
  • DOI: 10.1002/1873-3468.13506
  • Peer Reviewed / Open Access
• [Journal Article] Defective Epstein-Barr virus in chronic active infection and haematological malignancy. (2019)
  • Author(s): Okuno Y, Murata T, Sato Y,Yoshida K, Sawada A, Inoue M, Kawa K, Seto M, Ohshima K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Nishida T, Kiyoi H, Kato S, Nakamura S, Morishima S, Yoshikawa T, Fujiwara S, Shimizu N, Isobe Y, Noguchi M, Kikuta A, Iwatsuki K, Takahashi Y, Kojima S, Ogawa S, Kimura H.
  • Journal Title: Nat Microbiol. Volume: 4 Issue: 3 Pages: 404-413
  • DOI: 10.1038/s41564-018-0334-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells. (2019)
  • Author(s): Sakamoto A, Kunou S, Shimada K, Tsunoda M, Aoki T, Iriyama C, Tomita A, Nakamura S, Hayakawa F, Kiyoi H.
  • Journal Title: Cancer Sci Volume: 110 Issue: 1 Pages: 269-278
  • DOI: 10.1111/cas.13873
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of ASXL2 and ZBTB7A mutations and C-terminally truncated RUNX1-RUNX1T1 expression in AML patients with t(8;21) enrolled in the JALSG AML201 study. (2019)
  • Author(s): Kawashima N, Akashi A, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, Miyawaki S, Sakura T, Ozawa Y, Usui N, Kanamori H, Ito Y, Imai K, Suehiro Y, Kitamura K, Sakaida E, Takeshita A, Suzushima H, Naoe T, Matsumura I, Miyazaki Y, Ogawa S, Kiyoi H
  • Journal Title: Ann Hematol Volume: 98 Issue: 1 Pages: 83-91
  • DOI: 10.1007/s00277-018-3492-5
  • NAID: 120006623799
  • Peer Reviewed / Open Access
• [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
  • Journal Title: Leukemia Volume: 33 Issue: 2 Pages: 358-370
  • DOI: 10.1038/s41375-018-0233-7
  • Peer Reviewed / Open Access
• [Journal Article] Chromosomal translocation-mediated evasion from miRNA induces strong MEF2D fusion protein expression, causing inhibition of PAX5 transcriptional activity. (2019)
  • Author(s): Hirano D, Hayakawa F, Yasuda T, Tange N, Yamamoto H, Kojima Y, Morishita T, Imoto N, Tsuzuki S, Mano H, Naoe T, Kiyoi H.
  • Journal Title: Oncogene Volume: 38 Issue: 13 Pages: 2263-2274
  • DOI: 10.1038/s41388-018-0573-9
  • Peer Reviewed
• [Journal Article] Quantitative Assessment of T Cell Clonotypes in Human Acute Graft-versus-Host Disease Tissues. (2019)
  • Author(s): Koyama D, Murata M, Hanajiri R, Akashi T, Okuno S, Kamoshita S, Julamanee J, Takagi E, Miyao K, Sakemura R, Goto T, Terakura S, Nishida T, Kiyoi H
  • Journal Title: Biol Blood Marrow Transplant Volume: 25 Issue: 3 Pages: 417-423
  • DOI: 10.1016/j.bbmt.2018.10.012
  • Peer Reviewed / Open Access
• [Journal Article] Exome analysis of treatment-related AML after APL suggests secondary evolution (2018)
  • Author(s): Wang Tianjiao、Jacoby Meagan A.、Duncavage Eric J.、Miller Christopher A.、Heath Sharon、Rahme Ramy、Fenaux Pierre、Ades Lionel、Renneville Aline、Cassinat Bruno、Takeshita Akihiro、Asou Norio、Miyazaki Yasushi、Kiyoi Hitoshi、Ravandi Farhad、Westervelt Peter、Wartman Lukas D.、Welch John S.
  • Journal Title: British Journal of Haematology Volume: 印刷中 Issue: 5 Pages: 984-987
  • DOI: 10.1111/bjh.15681
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases. (2018)
  • Author(s): Li JF, Dai YT, Kubota Y, Kiyoi H, Matsumura I, Miyazaki Y, Olsson L, Tan AM, Ariffin H, Chen J, Takita J, Yasuda T, Mano H, Johansson B, Yang JJ, Yeoh AE, Hayakawa F, Chen Z, Pui CH, Fioretos T, Chen SJ, Huang JY.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 115 Issue: 50
  • DOI: 10.1073/pnas.1814397115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of the novel deletion-type PML-RARA mutation associated with the retinoic acid resistance in acute promyelocytic leukemia. (2018)
  • Author(s): Hattori H, Ishikawa Y, Kawashima N, Akashi A, Yamaguchi Y, Harada Y, Hirano D, Adachi Y, Miyao K, Ushijima Y, Terakura S, Nishida T, Matsushita T, Kiyoi H
  • Journal Title: PLoS One Volume: 13 Issue: 10 Pages: e0204850-e0204850
  • DOI: 10.1371/journal.pone.0204850
  • Peer Reviewed / Open Access
• [Journal Article] Biology and management of primary effusion lymphoma. (2018)
  • Author(s): Shimada K, Hayakawa F, Kiyoi H
  • Journal Title: Blood Volume: 132 Issue: 18 Pages: 1879-1888
  • DOI: 10.1182/blood-2018-03-791426
  • Peer Reviewed
• [Journal Article] Impact of hospital length of stay on the risk of readmission and overall survival after allogeneic stem cell transplantation. (2018)
  • Author(s): Seto A, Atsuta Y, Kawashima N, Ozawa Y, Miyamura K, Kiyoi H
  • Journal Title: Int J Hematol Volume: 108 Issue: 3 Pages: 290-297
  • DOI: 10.1007/s12185-018-2477-4
  • NAID: 120006536923
  • Peer Reviewed
• [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
  • Journal Title: Support Care Cancer Volume: 26 Issue: 12 Pages: 4187-4198
  • DOI: 10.1007/s00520-018-4292-0
  • Peer Reviewed / Open Access
• [Journal Article] Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response. (2018)
  • Author(s): Ueda N, Uemura Y, Zhang R, Kitayama S, Iriguchi S, Kawai Y, Yasui Y, Tatsumi M, Ueda T, Liu TY, Mizoro Y, Okada C, Watanabe A, Nakanishi M, Senju S, Nishimura Y, Kuzushima K, Kiyoi H, Naoe T, Kaneko S
  • Journal Title: Stem Cell Reports Volume: 10 Issue: 6 Pages: 1935-1946
  • DOI: 10.1016/j.stemcr.2018.04.025
  • NAID: 120006473765
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptional activities of DUX4 fusions in B-cell acute lymphoblastic leukemia (2018)
  • Author(s): Tanaka Yosuke、Kawazu Masahito、Yasuda Takahiko、Tamura Miki、Hayakawa Fumihiko、Kojima Shinya、Ueno Toshihide、Kiyoi Hitoshi、Naoe Tomoki、Mano Hiroyuki
  • Journal Title: Haematologica Volume: 103 Issue: 11 Pages: 522-526
  • DOI: 10.3324/haematol.2017.183152
  • Peer Reviewed / Open Access
• [Journal Article] Final analysis of the JALSG Ph+ALL202 study: tyrosine kinase inhibitor-combined chemotherapy for Ph+ALL (2018)
  • Author(s): Hatta Y, Mizuta S, Matsuo K, Ohtake S, Iwanaga M, Sugiura I, Doki N, Kanamori H, Ueda Y, Yoshida C, Dobashi N, Maeda T, Yujiri T, Monma F, Ito Y, Hayakawa F, Takeuchi J, Kiyoi H, Miyazaki Y, Naoe T
  • Journal Title: Ann Hematol Volume: 97 Issue: 9 Pages: 1535-1545
  • DOI: 10.1007/s00277-018-3323-8
  • Peer Reviewed / Open Access
• [Journal Article] Introduction of Genetically-Modified CD3ζ Improves Proliferation and Persistence of Antigen-specific CTLs. (2018)
  • Author(s): Miyao K, Terakura S, Okuno S, Julamanee J, Watanabe K, Hamana H, Kishi H, Sakemura R, Koyama D, Goto T, Nishida T, Murata M, Kiyoi H
  • Journal Title: Cancer Immunol Res Volume: 6 Pages: 733-744
  • Peer Reviewed
• [Journal Article] Mutation analysis of therapy-related myeloid neoplasms (2018)
  • Author(s): Nishiyama Takahiro、Ishikawa Yuichi、Kawashima Naomi、Akashi Akimi、Adachi Yoshiya、Hattori Hikaru、Ushijima Yoko、Kiyoi Hitoshi
  • Journal Title: Cancer Genetics Volume: 222 Pages: 38-45
  • DOI: 10.1016/j.cancergen.2018.02.006
  • Peer Reviewed
• [Journal Article] Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study (2018)
  • Author(s): Kobayashi Tomoko、Iwama Shintaro、Yasuda Yoshinori、Okada Norio、Tsunekawa Taku、Onoue Takeshi、Takagi Hiroshi、Hagiwara Daisuke、Ito Yoshihiro、Morishita Yoshiaki、Goto Motomitsu、Suga Hidetaka、Banno Ryoichi、Yokota Kenji、Hase Tetsunari、Morise Masahiro、Hashimoto Naozumi、Ando Masahiko、Kiyoi Hitoshi、et al.
  • Journal Title: J Endocr Soc. Volume: 2 Issue: 3 Pages: 241-251
  • DOI: 10.1210/js.2017-00432
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of the oligomeric states of nucleophosmin using size exclusion chromatography. (2018)
  • Author(s): Sakashita G, Kiyoi H, Naoe T, Urano T.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 4008-4008
  • DOI: 10.1038/s41598-018-22359-w
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study (2018)
  • Author(s): Harada Y、Nagata Y、Kihara R、Ishikawa Y、Asou N、Ohtake S、Miyawaki S、Sakura T、Ozawa Y、Usui N、Kanamori H、Ito Y、Imai K、Suehiro Y、Kobayashi S、Kitamura K、Sakaida E、Onizuka M、Takeshita A、Ishida F、Suzushima H、Ishizawa K、Naoe T、Matsumura I、Miyazaki Y、Ogawa S、Kiyoi H
  • Journal Title: Leukemia Research Volume: 66 Pages: 20-27
  • DOI: 10.1016/j.leukres.2018.01.008
  • NAID: 120006473597
  • Peer Reviewed
• [Journal Article] Distinct gene alterations with a high percentage of myeloperoxidase-positive leukemic blasts in de novo acute myeloid leukemia (2018)
  • Author(s): Kamijo Rena、Itonaga Hidehiro、Kihara Rika、Nagata Yasunobu、Hata Tomoko、Asou Norio、Ohtake Shigeki、Shiraishi Yuichi、Chiba Kenichi、Tanaka Hiroko、Miyano Satoru、Ogawa Seishi、Naoe Tomoki、Kiyoi Hitoshi、Miyazaki Yasushi
  • Journal Title: Leukemia Research Volume: 65 Pages: 34-41
  • DOI: 10.1016/j.leukres.2017.12.006
  • NAID: 120006988058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical effectiveness of geriatric assessment for predicting the tolerability of outpatient chemotherapy in older adults with cancer (2018)
  • Author(s): Hayashi Naomi、Matsuoka Ayumu、Goto Hidemi、Gotoh Momokazu、Kiyoi Hitoshi、Kodera Yasuhiro、Nagino Masato、Nagashima Fumio、Ando Yuichi
  • Journal Title: J Geriatr Oncol Volume: 9 Issue: 1 Pages: 84-86
  • DOI: 10.1016/j.jgo.2017.07.014
  • Peer Reviewed
• [Journal Article] High-dose methotrexate therapy significantly improved survival of adult acute lymphoblastic leukemia: a phase III study by JALSG (2017)
  • Author(s): Sakura T、Hayakawa F、Sugiura I、Murayama T、Imai K、Usui N、Fujisawa S、Yamauchi T、Yujiri T、Kakihana K、Ito Y、Kanamori H、Ueda Y、Miyata Y、Kurokawa M、Asou N、Ohnishi K、Ohtake S、Kobayashi Y、Matsuo K、Kiyoi H、Miyazaki Y、Naoe T
  • Journal Title: Leukemia Volume: 32 Issue: 3 Pages: 626-632
  • DOI: 10.1038/leu.2017.283
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia (2017)
  • Author(s): Kuwatsuka Y、Asou N、Ohtake S、Miyawaki S、Miyazaki Y、Sakura T、Ozawa Y、Usui N、Kanamori H、Ito Y、Imai K、Suehiro Y、Kobayashi S、Kitamura K、Sakaida E、Ogawa S、Naoe T、Hayashi Y、Horibe K、Manabe A、Mizutani S、Adachi S、Kiyoi H et al.
  • Journal Title: International Journal of Hematology Volume: 107 Issue: 2 Pages: 201-210
  • DOI: 10.1007/s12185-017-2340-z
  • NAID: 120006473552
  • Peer Reviewed
• [Journal Article] Deeper molecular response is a predictive factor for treatment-free remission after imatinib discontinuation in patients with chronic phase chronic myeloid leukemia: the JALSG-STIM213 study (2017)
  • Author(s): Takahashi Naoto、Miyata Yasuhiko、Kobayashi Shinichi、Usuki Kensuke、Matsumura Itaru、Minami Yosuke、Usui Noriko、Fukuda Tetsuya、Kobayashi Yukio、Kiyoi Hitoshi、et al.
  • Journal Title: Int J Hematol Volume: 107 Issue: 2 Pages: 185-193
  • DOI: 10.1007/s12185-017-2334-x
  • Peer Reviewed / Open Access
• [Journal Article] Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201 (2017)
  • Author(s): Harada Kaito、Doki Noriko、Hagino Takeshi、Miyawaki Shuichi、Ohtake Shigeki、Kiyoi Hitoshi、Miyazaki Yasushi、Fujita Hiroyuki、Usui Noriko、Okumura Hirokazu、Miyamura Koichi、Nakaseko Chiaki、Fujieda Atsushi、Nagai Tadashi、Yamane Takahisa、Sakamaki Hisashi、Ohnishi Kazunori、Naoe Tomoki、Ohno Ryuzo、Ohashi Kazuteru
  • Journal Title: Annals of Hematology Volume: 97 Issue: 1 Pages: 73-81
  • DOI: 10.1007/s00277-017-3156-x
  • Peer Reviewed
• [Journal Article] A novel irreversible FLT3 inhibitor, FF-10101, shows excellent efficacy against AML cells withFLT3mutations (2017)
  • Author(s): Yamaura Takeshi、Nakatani Toshiyuki、Uda Ken、Ogura Hayato、Shin Wigyon、Kurokawa Naoya、Saito Koichi、Fujikawa Norie、Date Tomomi、Takasaki Masaru、Terada Daisuke、Hirai Atsushi、Akashi Akimi、Chen Fangli、Adachi Yoshiya、Ishikawa Yuichi、Hayakawa Fumihiko、Hagiwara Shinji、Naoe Tomoki、Kiyoi Hitoshi
  • Journal Title: Blood Volume: 131 Issue: 4 Pages: 426-438
  • DOI: 10.1182/blood-2017-05-786657
  • Peer Reviewed
• [Journal Article] Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome (2017)
  • Author(s): Shirahata-Adachi Mizuho、Iriyama Chisako、Tomita Akihiro、Suzuki Yasuhiro、Shimada Kazuyuki、Kiyoi Hitoshi
  • Journal Title: Leuk Res Volume: 63 Pages: 90-97
  • DOI: 10.1016/j.leukres.2017.10.015
  • NAID: 120006473525
  • Peer Reviewed
• [Journal Article] Identification of volasertib-resistant mechanism and evaluation of combination effects with volasertib and other agents on acute myeloid leukemia (2017)
  • Author(s): Adachi Yoshiya、Ishikawa Yuichi、Kiyoi Hitoshi
  • Journal Title: Oncotarget Volume: 8 Issue: 45 Pages: 78452-78465
  • DOI: 10.18632/oncotarget.19632
  • Peer Reviewed / Open Access
• [Journal Article] High incidence of extensive chronic graft-versus-host disease in patients with the REG3A rs7588571 non-GG genotype (2017)
  • Author(s): Koyama Daisuke、Murata Makoto、Hanajiri Ryo、Okuno Shingo、Kamoshita Sonoko、Julamanee Jakrawadee、Takagi Erina、Hirano Daiki、Miyao Kotaro、Sakemura Reona、Goto Tatsunori、Hayakawa Fumihiko、Seto Aika、Ozawa Yukiyasu、Miyamura Koichi、Terakura Seitaro、Nishida Tetsuya、Kiyoi Hitoshi
  • Journal Title: PLoS One Volume: 12 Issue: 9 Pages: e0185213-e0185213
  • DOI: 10.1371/journal.pone.0185213
  • Peer Reviewed / Open Access
• [Journal Article] A nationwide survey of hypoplastic myelodysplastic syndrome (a multicenter retrospective study) (2017)
  • Author(s): Kobayashi T, Nannya Y, Ichikawa M, Oritani K, Kanakura Y, Tomita A, Kiyoi H, Kobune M, Kato J, Kawabata H, Shindo M, Torimoto Y, Yonemura Y, Tohyama K, et al
  • Journal Title: American Journal of Hematology Volume: 92 Issue: 12 Pages: 1324-1332
  • DOI: 10.1002/ajh.24905
  • Peer Reviewed / Open Access
• [Journal Article] Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group (2017)
  • Author(s): Kimura Shun-ichi、JFujita Hiroyuki、Kato Hideaki、Hiramoto Nobuhiro、Hosono Naoko、Takahashi Tsutomu、Shigeno Kazuyuki、Hatsumi Naoko、Minamiguchi Hitoshi、Miyatake Junichi、Handa Hiroshi、Akiyama Nobu、Kanda Yoshinobu、Yoshida Minoru、Kiyoi Hitoshi、et al.
  • Journal Title: Support Care Cancer Volume: 25 Issue: 11 Pages: 3515-3521
  • DOI: 10.1007/s00520-017-3775-8
  • Peer Reviewed
• [Journal Article] Phase II study of intrabone single unit cord blood transplantation for hematological malignancies (2017)
  • Author(s): Murata Makoto、Maeda Yoshinobu、Masuko Masayoshi、et.al
  • Journal Title: Cancer Science Volume: 108 Issue: 8 Pages: 1634-1639
  • DOI: 10.1111/cas.13291
  • Peer Reviewed / Open Access
• [Journal Article] Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia. (2017)
  • Author(s): Togasaki E, Takeda J, Yoshida K, Shiozawa Y, Takeuchi M, Kiyoi H, Ohnishi K, Ohtake S, Asou N, Kobayashi Y, Miyazaki Y, Miyano S, Ogawa S, Matsumura I, Nakaseko C, Naoe T.
  • Journal Title: Blood Cancer J. Volume: 7 Issue: 4 Pages: 2017-2017
  • DOI: 10.1038/bcj.2017.36
  • Peer Reviewed / Open Access
• [Journal Article] YM155 induces apoptosis through proteasome-dependent degradation of MCL-1 in primary effusion lymphoma. (2017)
  • Author(s): Kojima Y, Hayakawa F, Morishita T, Sugimoto K, Minamikawa Y, Iwase M, Yamamoto H, Hirano D, Imoto N, Shimada K, Okada S, Kiyoi H
  • Journal Title: Pharmacol Res. Volume: in press Pages: 242-251
  • DOI: 10.1016/j.phrs.2017.04.006
  • Peer Reviewed / Open Access
• [Journal Article] Impact of T-cell chimerism on relapse after cord blood transplantation for hematological malignancies: Nagoya Blood and Marrow Transplantation Group study (2017)
  • Author(s): Yokohata E, Kuwatsuka Y, Ohashi H, Terakura S, Kawashima N, Seto A, Kurahashi S, Ozawa Y, Goto T, Imahashi N, Nishida T, Miyao K, Sakemura R, Kato T, Sawa M, Kohno A, Sao H, Iida H, Kiyoi H, Naoe T, Miyamura K, Murata M
  • Journal Title: Bone Marrow Transplant. Volume: in press Issue: 4 Pages: 612-614
  • DOI: 10.1038/bmt.2016.323
  • Peer Reviewed
• [Presentation] FLT3変異陽性AML細胞における野生型FLT3の発現とFLT3阻害剤の阻害活性 (2019)
  • Author(s): 金貞姫, 石川裕一, 川島直実, 中島麻梨絵, 原田靖彦, 牛島洋子, 清井仁
  • Organizer: 日本血液学会年次総会
• [Presentation] FLT3-ITD 変異陽性AML に対する第一寛解期での同種造血幹細胞移植； JALSG AML209-FLT3-SCT Study 結果 (2019)
  • Author(s): 川島直実, 石川裕一, 熱田由子, 澤正史, 小澤幸泰, 林正樹, 河野彰夫, 冨田章裕,前田智也, 堺田惠美子, 臼杵憲祐, 萩原真紀, 金森平和, 松岡広, 小林美希,麻生範雄, 大竹茂樹, 松村到, 宮﨑泰司, 直江知樹, 清井仁
  • Organizer: 日本血液学会年次総会
• [Presentation] 急性骨髄性白血病に対するレセプター型チロシンキナーゼの細胞膜発現阻害薬の開発とその有効性 (2019)
  • Author(s): 中島麻梨絵, 江嵜正浩, 石川裕一, 川島直実, 金貞姫, 原田靖彦, 牛島洋子, 石井俊彦, 森聖寿, 清井仁
  • Organizer: 日本血液学会年次総会
• [Presentation] 急性骨髄性白血病白血病に対するクリニカルシークエンス実行可能性を検証する多施設共同研究 (2019)
  • Author(s): 横山寿行, 安田貴彦, 石川裕一, 臼杵憲祐, 矢野真吾, 伊藤良和, 康史朗, 木口亨, 宮田泰彦, 清井仁, 松村到, 宮﨑泰司, 服部浩佳, 西島大, 山本松雄, 齋藤明子, 倉橋浩樹, 白石友一, 宮野悟, 真田昌, 小川誠司, 堀部敬三
  • Organizer: 日本血液学会年次総会
• [Presentation] AMLにおけるFLT3阻害剤の効果予測バイオマーカーと至適治療法の開発 (2019)
  • Author(s): 原田靖彦, 石川裕一, 川島直実, 金貞姫, 中島麻梨絵, 足立佳也, 牛島洋子, 清井仁
  • Organizer: 日本血液学会年次総会
• [Presentation] Development of Predictive Biomarker and Optimal Treatment Strategy with FLT3 Inhibitors in Acute Myeloid Leukemia (2019)
  • Author(s): Jeong Hui Kim, Yasuhiko Harada, Yuichi Ishikawa, Naomi Kawashima, Marie Nakashima, Yoko Ushijima, Takahiro Nishiyama, Tatsunori Goto, Nobuaki Fukushima, Rika Kihara, Tomohiro Kajiguchi, Koichi Watamoto, Akio Kohno, Kunio Kitamura, Yukiyasu Ozawa, Hitoshi Kiyoi
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] Prospective Evaluation of Allogeneic HSCT at the First Remission for Younger Adults with FLT3 -ITD Positive Acute Myeloid Leukemia: The JALSG AML209-FLT3-SCT Study (2019)
  • Author(s): Naomi Kawashima, Yuichi Ishikawa, Yoshiko Atsuta, Hitoshi Kiyoi
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] Phase I Study of Cord Blood Transplantation with Intra-Bone Marrow Injection of Mesenchymal Stem Cells (2019)
  • Author(s): Tatsunori Goto, Makoto Murata, Tetsuya Nishida, Seitaro Terakura, Sonoko Kamoshita, Yuichi Ishikawa, Yoko Ushijima, Yoshiya Adachi, Katsuyoshi Kato, Akihiro Hirakawa, Satoshi Nishiwaki, Nobuhiro Nishio, Yoshiyuki Takahashi, Yoshihisa Kodera, Tadashi Matsushita, Hitoshi Kiyoi
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] Staurosporine Induces Caspase-Dependent Proteolysis of MEF2D-Fusion Protein and Cell Death Selective to MEF2D-Fusion-Positive ALL Cells (2019)
  • Author(s): Naoyuki Tange, Fumihiko Hayakawa, Takahiko Yasuda, Hideyuki Yamamoto, Daiki Hirano, Shinobu Tsuzuki, Hitoshi Kiyoi
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] Guided Polarization of iPSC-Derived CD4SP Helper T Cells By CRISPR/Cas9-Based Genome-Editing (2019)
  • Author(s): Hisashi Yano, Tokuyuki Shinohara, Keiko Koga, Shoichi Iriguchi, Yasuyuki Miyake, Xuewei Song, Megumi Tada, Yoshiaki Kassai, Hitoshi Kiyoi, Shin Kaneko
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] FF-10101 Retains Potent Inhibitory Activities Against Resistant Mutations to FLT3 Inhibitors, Newly Identified in Random Mutagenesis Screens (2019)
  • Author(s): Yuichi Ishikawa, Koichi Saito, Naomi Kawashima, Michie Morimoto, Hidetoshi Murao, Daisuke Terada, Takeshi Yamaura, Shinji Hagiwara, Hitoshi Kiyoi
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] Discovery of a Novel Dihydroorotate Dehydrogenase Inhibitor That Induces Differentiation and Overcomes Ara-C Resistance of Acute Myeloid Leukemia Cells (2019)
  • Author(s): Satoshi Kitazawa, Yukiko Ishii, Keiko Makita-Suzuki, Koichi Saito, Kensuke Takayanagi, Hiromi Sugihara, Shun Matsuda, Takayuki Yamakawa, Yasuhiro Tsutsui, Tadashi Tanaka, Tomohisa Hatta, Tohru Natsume, Toru Kondo, Yuichi Ishikawa, Shinji Hagiwara, Hitoshi Kiyoi
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] Favorable Outcomes of Newly Diagnosed Intravascular Large B-Cell Lymphoma Patients Treated with R-CHOP Combined with High-Dose Methotrexate Plus Intrathecal Chemotherapy: Results from a Multicenter Phase 2 Trial (PRIMEUR-IVL) (2019)
  • Author(s): Kazuyuki Shimada, Hitoshi Kiyoi, Ritsuro Suzuki, Takashi Tokunaga, Shigeo Nakamura, Tomohiro Kinoshita
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] Prospective Comparison of Azacitidine Treatment between 7-Days and 5-Days Schedules for Patients with Higher-Risk Myelodysplastic Syndromes; Results of Japan Adult Leukemia Study Group MDS212 Trial (2019)
  • Author(s): Toru Kiguchi, Hitoshi Kiyoi, Tomoki Naoe, Yasushi Miyazaki
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] The Optimal Treatment Strategy for Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in First Complete Remission in the Era of High-Intensity Chemotherapy (2019)
  • Author(s): Shinichi Kako,Hitoshi Kiyoi, Itaru Matsumura, Yasushi Miyazaki, Yoshiko Atsuta
  • Organizer: 米国血液学会年次総会
  • Int'l Joint Research
• [Presentation] Clinical significance of ASXL2 and ZBTB7A mutations and AML1-ETO9a expression in AML with t(8;21): the JALSG AML201 study. (2018)
  • Author(s): Kawashima N, Ishikawa Y, Kiyoi H, Atsuta Y, Ohtake S, Asou N, Miyazaki Y
  • Organizer: 第37回 International Society of Hematology. Annual Meeting
  • Int'l Joint Research
• [Presentation] Prospective Evaluation of Prognostic Relevance of KIT Mutations in Core-Binding Factor Acute Myeloid Leukemia: Results from the JALSG CBF-AML209-KIT Study (2018)
  • Author(s): Kawashima N, Ishikawa Y, Kiyoi H, Atsuta Y, Ohtake S, Asou N, Miyazaki Y
  • Organizer: 第60回 American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Dynamics of Genetic Landscapes and Clonal Evolution between Patients and PDX Models in Acute Myeloid Leukemia. (2018)
  • Author(s): Kawashima N, Ishikawa Y, Kiyoi H
  • Organizer: 第60回 American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] High expression of MEF2D-fusion protein by escaping from the regulation by microRNA (2017)
  • Author(s): Daiki Hirano, Fumihiko Hayakawa, Takahiko Yasuda, naoyuki Tange, Hideyuki Yamamoto, Yuki Kojima, Takanobu Morishita, Naoto Imoto, Shinobu Tsuzuki, Hiroyuki Mano, Tomoki Naoe, Hitoshi Kiyoi
  • Organizer: 59th annual meeting of american society of hematology
  • Int'l Joint Research
• [Presentation] Clonal Analysis of Acute Myeloid Leukemia secondary to Myeloproliferative Neoplasms (2017)
  • Author(s): Yoko Ushijima, Yuichi Ishikawa, Hikaru Hattori, Naomi Kawashima, Shun Fujiwara, Seitaro Terakura, Masashi Sanada, Hitoshi Kiyoi
  • Organizer: 59th annual meeting of american society of hematology
  • Int'l Joint Research