Updated on 2021/11/04

写真a

 
HAYAKAWA, Fumihiko
 
Organization
Graduate School of Medicine Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Health Sciences
Title
Professor

Degree 1

  1. 医学博士 ( 2001.3   名古屋大学 ) 

Research Interests 7

  1. Drug screening

  2. Genetic analysis

  3. Pathophysiological analysis

  4. Multi-agent clinical trial

  5. Clinical trial

  6. Malignant lymphoma

  7. Leukemia

Research Areas 1

  1. Life Science / Pharmaceutical chemistry and drug development sciences

Current Research Project and SDGs 5

  1. 急性リンパ性白血病で認められる遺伝子異常の白血病発症機序の解明

  2. 急性リンパ性白血病遺伝子解析

  3. 急性リンパ芽球性白血病に対する最適な化学療法の検討

  4. プライマリ腫瘍細胞を用いた新規薬剤スクリーニング方法の開発

  5. PAX5遺伝子変異による急性リンパ性白血病発症機構の解明

Research History 8

  1. 名古屋大学大学院医学系研究科   医療技術学専攻病態解析学講座   教授

    2018.4

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    Country:Japan

  2. 名古屋大学医学部附属病院   血液内科   講師

    2016.5

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    Country:Japan

  3. 名古屋大学医学部附属病院    血液内科   助教

    2010.4 - 2016.4

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    Country:Japan

  4. 名古屋大学医学系研究科 GCOE特任講師

    2008.11 - 2009.3

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    Country:Japan

  5. 名古屋大学医学部附属病院 血液・腫瘍内科学 医員

    2005.4 - 2008.10

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    Country:Japan

  6. 医師 豊橋市民病院

    2004.6 - 2005.3

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    Country:Japan

  7. Postdoctoral fellow, Department of Microbiology, University of California, Davis

    2001.5 - 2004.4

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    Country:United States

  8. 医師 安城更正病院

    1993.5 - 1996.3

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    Country:Japan

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Education 2

  1. Nagoya University

    1996.4 - 2000.3

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1987.4 - 1993.3

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    Country: Japan

Professional Memberships 3

  1. 日本血液学会   ガイドライン委員

  2. 日本内科学会

  3. 日本癌学会

Committee Memberships 2

  1. 日本血液学会   ガイドライン委員  

    2015.10   

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    Committee type:Academic society

  2. 日本血液学会   IJH編集委員  

    2019.10   

Awards 1

  1. 上原記念生命科学財団 研究奨励金

    2006   上原記念生命科学財団  

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    Country:Japan

 

Papers 79

  1. Two novel high-risk adult B-cell acute lymphoblastic leukemia subtypes with high expression of CDX2 and IDH1/2 mutations.

    Yasuda T, Sanada M, Kawazu M, Kojima S, Tsuzuki S, Ueno H, Iwamoto E, Iijima-Yamashita Y, Yamada T, Kanamori T, Nishimura R, Kuwatsuka Y, Takada S, Tanaka M, Ota S, Dobashi N, Yamazaki E, Hirose A, Murayama T, Sumi M, Sato S, Tange N, Nakamura Y, Katsuoka Y, Sakaida E, Kawamata T, Iida H, Shiraishi Y, Nannya Y, Ogawa S, Taniwaki M, Asou N, Hatta Y, Kiyoi H, Matsumura I, Horibe K, Mano H, Naoe T, Miyazaki Y, Hayakawa F

    Blood     2021.10

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    Authorship:Last author, Corresponding author   Language:English  

    DOI: 10.1182/blood.2021011921

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  2. Targeting MEF2D-fusion oncogenic transcriptional circuitries in B-cell precursor acute lymphoblastic leukemia Reviewed

    Tsuzuki S, Yasuda T, Kojima S, Kawazu M, Akahane K, Inukai T, Imaizumi M, Morishita T, Miyamura K, Ueno T, Karnan S, Ota A, Hyodo T, Konishi H, Sanada M, Nagai H, Horibe K, Tomita A, Suzuki K, Muramatsu H, Takahashi Y, Miyazaki Y, Matsumura I, Kiyoi H, Hosokawa Y, Mano H, Hayakawa F

    Blood Cancer Discovery   Vol. 1 ( 1 ) page: 82 - 95   2020.7

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    Authorship:Last author   Language:English   Publishing type:Research paper (scientific journal)  

  3. Chromosomal translocation-mediated evasion from miRNA induces strong MEF2D fusion protein expression, causing inhibition of PAX5 transcriptional activity Reviewed

    Hirano Daiki, Hayakawa Fumihiko, Yasuda Takahiko, Tange Naoyuki, Yamamoto Hideyuki, Kojima Yuki, Morishita Takanobu, Imoto Naoto, Tsuzuki Shinobu, Mano Hiroyuki, Naoe Tomoki, Kiyoi Hitoshi

    ONCOGENE   Vol. 38 ( 13 ) page: 2263-2274   2019.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41388-018-0573-9

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  4. Optimal treatment for Philadelphia-negative acute lymphoblastic leukemia in first remission in the era of high-intensity chemotherapy

    Kako Shinichi, Hayakawa Fumihiko, Imai Kiyotoshi, Tanaka Junji, Mizuta Shuichi, Nishiwaki Satoshi, Kanamori Heiwa, Mukae Junichi, Ozawa Yukiyasu, Kondo Tadakazu, Fukuda Takahiro, Ichinohe Tatsuo, Ota Shuichi, Tanaka Yoshinori, Murayama Tohru, Kurahashi Shingo, Sakura Toru, Usui Noriko, Ohtake Shigeki, Kiyoi Hitoshi, Matsumura Itaru, Miyazaki Yasushi, Atsuta Yoshiko

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 114 ( 5 ) page: 608 - 619   2021.11

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  5. Dasatinib-based Two-step Induction for Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

    Sugiura I, Doki N, Hata T, Cho R, Ito T, Suehiro Y, Tanaka M, Kako S, Matsuda M, Yokoyama H, Ishikawa Y, Taniguchi Y, Hagihara M, Ozawa Y, Ueda Y, Hirano D, Sakura T, Tsuji M, Kamae T, Fujita H, Hiramoto N, Onoda M, Fujisawa S, Hatta Y, Dobashi N, Nishiwaki S, Atsuta Y, Kobayashi Y, Hayakawa F, Ohtake S, Naoe T, Miyazaki Y

    Blood advances     2021.9

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    Language:English  

    DOI: 10.1182/bloodadvances.2021004607

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  6. Exosomes secreted from cancer-associated fibroblasts elicit anti-pyrimidine drug resistance through modulation of its transporter in malignant lymphoma

    Kunou Shunsuke, Shimada Kazuyuki, Takai Mika, Sakamoto Akihiko, Aoki Tomohiro, Hikita Tomoya, Kagaya Yusuke, Iwamoto Eisuke, Sanada Masashi, Shimada Satoko, Hayakawa Fumihiko, Oneyama Chitose, Kiyoi Hitoshi

    ONCOGENE   Vol. 40 ( 23 ) page: 3989 - 4003   2021.6

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  7. Essential role of a carboxyl-terminal alpha-helix motif in the secretion of coagulation factor XI

    Hayakawa Yuri, Tamura Shogo, Suzuki Nobuaki, Odaira Koya, Tokoro Mahiru, Kawashima Fumika, Hayakawa Fumihiko, Takagi Akira, Katsumi Akira, Suzuki Atsuo, Okamoto Shuichi, Kanematsu Takeshi, Matsushita Tadashi, Kojima Tetsuhito

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS   Vol. 19 ( 4 ) page: 920 - 930   2021.4

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  8. 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

    Saito Takeshi, Hatta Yoshihiro, Hayakawa Fumihiko, Takahashi Tsutomu, Hagihara Maki, Iida Hiroatsu, Minauchi Koichiro, Yamazaki Etsuko, Sugiura Isamu, Murayama Tohru, Sakura Toru, Mori Naoki, Imai Kiyotoshi, Yahagi Yuichi, Atsuta Yoshiko, Saito Akiko Moriya, Hirakawa Akihiro, Kiyoi Hitoshi, Matsumura Itaru, Miyazaki Yasushi

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 113 ( 3 ) page: 395 - 403   2021.3

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  9. Exosomes derived from cancer associated fibroblasts induce a resistance to histone deacetylase inhibitors in lymphoma

    Kagaya Yusuke, Shimada Kazuyuki, Kunou Shunsuke, Hikita Tomoya, Sakamoto Akihiko, Hayakawa Fumihiko, Oneyama Chitose, Kiyoi Hitoshi

    CANCER SCIENCE   Vol. 112   page: 370 - 370   2021.2

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    Language:Japanese  

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  10. [B cell acute lymphoblastic leukemia therapy: an up to date overview].

    Hayakawa F

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 62 ( 8 ) page: 1094 - 1101   2021

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    Language:Japanese  

    DOI: 10.11406/rinketsu.62.1094

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  11. Functional analysis of a novel fusion protein PAX5-KIDINS220 identified in a pediatric Ph-like ALL patient

    Kanayama Takuyo, Imamura Toshihiko, Mayumi Azusa, Soma Emi, Sakamoto Kenichi, Hayakawa Fumihiko, Tanizawa Akihiko, Kiyokawa Nobutaka, Hosoi Hajime

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 112 ( 5 ) page: 714 - 719   2020.11

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-020-02944-4

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  12. JSH practical guidelines for hematological malignancies, 2018: I. leukemia-3. acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL)

    Hatta Yoshihiro, Hayakawa Fumihiko, Yamazaki Etsuko

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 112 ( 4 ) page: 439 - 458   2020.10

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  13. Aberrant X chromosomal rearrangement through multi-step template switching during sister chromatid formation in a patient with severe hemophilia A

    Tokoro Mahiru, Tamura Shogo, Suzuki Nobuaki, Kakihara Misaki, Hattori Yuna, Odaira Koya, Suzuki Sachiko, Takagi Akira, Katsumi Akira, Hayakawa Fumihiko, Okamoto Shuichi, Suzuki Atsuo, Kanematsu Takeshi, Matsushita Tadashi, Kojima Tetsuhito

    MOLECULAR GENETICS & GENOMIC MEDICINE   Vol. 8 ( 9 ) page: e1390   2020.9

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/mgg3.1390

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  14. Staurosporine and venetoclax induce the caspase-dependent proteolysis of MEF2D-fusion proteins and apoptosis in MEF2D-fusion (+) ALL cells. Reviewed

    Tange N, Hayakawa F, Yasuda T, Odaira K, Yamamoto H, Hirano D, Sakai T, Terakura S, Tsuzuki S, Kiyoi H

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   Vol. 128   page: 110330   2020.8

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.biopha.2020.110330

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  15. A case of pemphigus with anti-desmoglein 3 and anti-desmocollin 2 and 3 autoantibodies, associated with follicular lymphoma and bronchiolitis obliterans.

    Yoshikawa M, Takeichi T, Taki T, Hayakawa F, Ishii N, Hashimoto T, Muro Y, Akiyama M

    European journal of dermatology : EJD   Vol. 30 ( 4 ) page: 424 - 425   2020.7

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1684/ejd.2020.3812

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  16. Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia.

    Tsuzuki S, Yasuda T, Kojima S, Kawazu M, Akahane K, Inukai T, Imaizumi M, Morishita T, Miyamura K, Ueno T, Karnan S, Ota A, Hyodo T, Konishi H, Sanada M, Nagai H, Horibe K, Tomita A, Suzuki K, Muramatsu H, Takahashi Y, Miyazaki Y, Matsumura I, Kiyoi H, Hosokawa Y, Mano H, Hayakawa F

    Blood cancer discovery   Vol. 1 ( 1 ) page: 82 - 95   2020.7

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    Language:English  

    DOI: 10.1158/2643-3230.BCD-19-0080

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  17. High prevalence of MEF2D fusion in human B-cell precursor acute lymphoblastic leukemia cell lines. Reviewed

    Akahane K, Yasuda T, Tsuzuki S, Hayakawa F, Kiyokawa N, Somazu S, Watanabe A, Kagami K, Abe M, Harama D, Goi K, Kawazu M, Kojima S, Imamura T, Goto H, Iwamoto S, Minegishi M, Abe M, Hojo H, Inaba T, Mano H, Sugita K, Inukai T

    Hematological oncology     2020.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/hon.2762

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  18. Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells Reviewed

    Inoue Chisato, Sobue Sayaka, Kawamoto Yoshiyuki, Nishizawa Yuji, Ichihara Masatoshi, Abe Akihiro, Hayakawa Fumihiko, Suzuki Motoshi, Nozawa Yoshinori, Murate Takahsi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 525 ( 4 ) page: 1074 - 1080   2020.5

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2020.02.165

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  19. Vaticanol C, a phytoalexin, induces apoptosis of leukemia and cancer cells by modulating expression of multiple sphingolipid metabolic enzymes Reviewed

    Inoue Chisato, Sobue Sayaka, Mizutani Naoki, Kawamoto Yoshiyuki, Nishizawa Yuji, Ichihara Masatoshi, Takeuchi Toshiyuki, Hayakawa Fumihiko, Suzuki Motoshi, Ito Tetsuro, Nozawa Yoshinori, Murate Takashi

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 82 ( 2 ) page: 261-280   2020.5

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    DOI: 10.18999/nagjms.82.2.261

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  20. Higher FVIII:C measured by chromogenic substrate assay than by one-stage assay is associated with silent hemophilic arthropathy Reviewed

    Ogawa Mika, Suzuki Nobuaki, Takahashi Nobunori, Tamura Shogo, Suzuki Atsuo, Suzuki Sachiko, Hattori Yuua, Kakihara Misaki, Kanematsu Takeshi, Kojima Toshihisa, Katsumi Akira, Hayakawa Fumihiko, Kojima Tetsuhito, Ishiguro Naoki, Kiyoi Hitoshi, Matsushita Tadashi

    THROMBOSIS RESEARCH   Vol. 188   page: 103 - 105   2020.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.thromres.2020.01.003

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  21. ZNF384-fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities Reviewed

    Yamamoto Hideyuki, Hayakawa Fumihiko, Yasuda Takahiko, Odaira Koya, Minamikawa Yuka, Tange Naoyuki, Hirano Daiki, Kojima Yuki, Morishita Takanobu, Tsuzuki Shinobu, Naoe Tomoki, Kiyoi Hitoshi

    FEBS LETTERS   Vol. 593 ( 16 ) page: 2151 - 2161   2019.8

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    DOI: 10.1002/1873-3468.13506

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  22. Apparent synonymous mutation F9 c.87A > G causes secretion failure by in-frame mutation with aberrant splicing Reviewed

    Odaira Koya, Tamura Shogo, Suzuki Nobuaki, Kakihara Misaki, Hattori Yuna, Tokoro Mahiru, Suzuki Sachiko, Takagi Akira, Katsumi Akira, Hayakawa Fumihiko, Okamoto Shuichi, Suzuki Atsuo, Kanematsu Takeshi, Matsushita Tadashi, Kojima Tetsuhito

    THROMBOSIS RESEARCH   Vol. 179   page: 95 - 103   2019.7

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    DOI: 10.1016/j.thromres.2019.04.022

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  23. Molecular basis of SERPINC1 mutations in Japanese patients with antithrombin deficiency Reviewed

    Tamura Shogo, Hashimoto Erika, Suzuki Nobuaki, Kakihara Misaki, Odaira Koya, Hattori Yuna, Tokoro Mahiru, Suzuki Sachiko, Takagi Akira, Katsumi Akira, Hayakawa Fumihiko, Suzuki Atsuo, Okamoto Shuichi, Kanematsu Takeshi, Matsushita Tadashi, Kojima Tetsuhito

    THROMBOSIS RESEARCH   Vol. 178   page: 159 - 170   2019.6

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    DOI: 10.1016/j.thromres.2019.04.004

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  24. [Peri-arteriolar megakaryopoietic microenvironment via reciprocal CLEC-2/PDPN axis in bone marrow]. Invited Reviewed

    Tamura S, Suzuki-Inoue K, Ozaki Y, Hayakawa F, Kojima T

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 60 ( 7 ) page: 834-842   2019

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    DOI: 10.11406/rinketsu.60.834

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  25. Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases Reviewed

    Li Jian-Feng, Dai Yu-Ting, Lilljebjorn Henrik, Shen Shu-Hong, Cui Bo-Wen, Bai Ling, Liu Yuan-Fang, Qian Mao-Xiang, Kubota Yasuo, Kiyoi Hitoshi, Matsumura Itaru, Miyazaki Yasushi, Olsson Linda, Tan Ah Moy, Ariffin Hany, Chen Jing, Takita Junko, Yasuda Takahiko, Mano Hiroyuki, Johansson Bertil, Yang Jun J., Yeoh Allen Eng-Juh, Hayakawa Fumihiko, Chen Zhu, Pui Ching-Hon, Fioretos Thoas, Chen Sai-Juan, Huang Jin-Yan

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   Vol. 115 ( 50 ) page: E11711-E11720   2018.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.1814397115

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  26. Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells.

    Sakamoto A, Kunou S, Shimada K, Tsunoda M, Aoki T, Iriyama C, Tomita A, Nakamura S, Hayakawa F, Kiyoi H

    Cancer science     2018.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.13873

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  27. Biology and management of primary effusion lymphoma.

    Shimada K, Hayakawa F, Kiyoi H

    Blood   Vol. 132 ( 18 ) page: 1879-1888   2018.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2018-03-791426

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  28. Transcriptional activities of DUX4 fusions in B-cell acute lymphoblastic leukemia.

    Tanaka Y, Kawazu M, Yasuda T, Tamura M, Hayakawa F, Kojima S, Ueno T, Kiyoi H, Naoe T, Mano H

    Haematologica   Vol. 103 ( 11 ) page: e522-e526   2018.11

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    DOI: 10.3324/haematol.2017.183152

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  29. Final analysis of the JALSG Ph+ALL202 study: tyrosine kinase inhibitor-combined chemotherapy for Ph plus ALL

    Hatta Yoshihiro, Mizuta Shuichi, Matsuo Keitaro, Ohtake Shigeki, Iwanaga Masako, Sugiura Isamu, Doki Noriko, Kanamori Heiwa, Ueda Yasunori, Yoshida Chikamasa, Dobashi Nobuaki, Maeda Tomoya, Yujiri Toshiaki, Monma Fumihiko, Ito Yoshikazu, Hayakawa Fumihiko, Takeuchi Jin, Kiyoi Hitoshi, Miyazaki Yasushi, Naoe Tomoki

    ANNALS OF HEMATOLOGY   Vol. 97 ( 9 ) page: 1535-1545   2018.9

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    DOI: 10.1007/s00277-018-3323-8

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  30. BCL2 inhibitor ABT-199 and JNK inhibitor SP600125 exhibit synergistic cytotoxicity against imatinib-resistant Ph+ ALL cells.

    Inoue C, Sobue S, Aoyama Y, Mizutani N, Kawamoto Y, Nishizawa Y, Ichihara M, Abe A, Hayakawa F, Suzuki M, Nozawa Y, Murate T

    Biochemistry and biophysics reports   Vol. 15   page: 69 - 75   2018.9

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    DOI: 10.1016/j.bbrep.2018.07.001

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  31. Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells: A clinical study protocol

    Goto Tatsunori, Murata Makoto, Terakura Seitaro, Nishida Tetsuya, Adachi Yoshiya, Ushijima Yoko, Shimada Kazuyuki, Ishikawa Yuichi, Hayakawa Fumihiko, Nishio Nobuhiro, Nishiwaki Satoshi, Hirakawa Akihiro, Kato Katsuyoshi, Takahashi Yoshiyuki, Kiyoi Hitoshi

    MEDICINE   Vol. 97 ( 17 ) page: e0449   2018.4

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    DOI: 10.1097/MD.0000000000010449

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  32. High Incidence of Extensive Chronic Gvhd in Patients with the REG3A Rs7588571 Non-GG Genotype

    Murata Makoto, Koyama Daisuke, 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

    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION   Vol. 24 ( 3 ) page: S192-S193   2018.3

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  33. High-dose methotrexate therapy significantly improved survival of adult acute lymphoblastic leukemia: a phase III study by JALSG

    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.

    LEUKEMIA   Vol. 32 ( 3 ) page: 626-632   2018.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/leu.2017.283

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  34. A novel irreversible FLT3 inhibitor, FF-10101, shows excellent efficacy against AML cells with FLT3 mutations

    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

    BLOOD   Vol. 131 ( 4 ) page: 426-438   2018.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2017-05-786657

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  35. [Adult acute lymphoblastic leukemia: update on pathophysiology and management].

    Hayakawa F

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 59 ( 5 ) page: 497 - 503   2018

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.11406/rinketsu.59.497

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  36. The transcriptional landscape of B-cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases Reviewed

    Jian-Feng Li, Yu-Ting Dai, Henrik Lilljebjörn, Shu-Hong Shen, Bo-Wen Cui, Ling Bai, Yuan-Fang Liu, Mao-Xiang Qian, Yasuo Kubota, Hitoshi Kiyoi, Itaru Matsumura, Yasushi Miyazaki, Linda Olsson, Ah Moy Tan, Hany Ariffin, Jing Chen, Junko Takita, Takahiko Yasuda, Hiroyuki Mano, Bertil Johansson, Jun J. Yang, Allen Eng-Juh Yeoh, Fumihiko Hayakawa, Zhu Chen, Ching-Hon Pui, Thoas Fioretos, Sai-Juan Chen, Jin-Yan Huang

    Proceedings of the National Academy of Sciences of the United Stats of America   Vol. in press ( in press ) page: in press   2018

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  37. High incidence of extensive chronic graft-versus-host disease in patients with the REG3A rs7588571 non-GG genotype

    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

    PLOS ONE   Vol. 12 ( 9 ) page: e0185213   2017.9

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    DOI: 10.1371/journal.pone.0185213

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  38. YM155 induces apoptosis through proteasome-dependent degradation of MCL-1 in primary effusion lymphoma

    Kojima Yuki, Hayakawa Fumihiko, Morishita Takanobu, Sugimoto Keiki, Minamikawa Yuka, Iwase Mizuho, Yamamoto Hideyuki, Hirano Daiki, Imoto Naoto, Shimada Kazuyuki, Okada Seiji, Kiyoi Hitoshi

    PHARMACOLOGICAL RESEARCH   Vol. 120   page: 242-251   2017.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.phrs.2017.04.006

    Web of Science

    PubMed

  39. Emetine elicits apoptosis of intractable B-cell lymphoma cells with MYC rearrangement through inhibition of glycolytic metabolism

    Aoki Tomohiro, Shimada Kazuyuki, Sakamoto Akihiko, Sugimoto Keiki, Morishita Takanobu, Kojima Yuki, Shimada Satoko, Kato Seiichi, Iriyama Chisako, Kuno Shunsuke, Harada Yasuhiko, Tomita Akihiro, Hayakawa Fumihiko, Kiyoi Hitoshi

    ONCOTARGET   Vol. 8 ( 8 ) page: 13085 - 13098   2017.2

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.18632/oncotarget.14393

    Web of Science

    PubMed

  40. Acute lymphoblastic leukemia of adolescents and young adults: from the viewpoint of physicians.

    Yasuda T, Hayakawa F

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 58 ( 8 ) page: 1031-1037   2017

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.11406/rinketsu.58.1031

    PubMed

  41. Malignant lymphoma with cardiac involvement.

    Terakura S, Onji M, Iriyama C, Goto T, Ushijima Y, Shimada K, Ishikawa Y, Nishida T, Hayakawa F, Murata M, Kiyoi H

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 58 ( 3 ) page: 239-242   2017

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.11406/rinketsu.58.239

    PubMed

  42. The photosensitizer verteporfin has light-independent anti-leukemic activity for Ph-positive acute lymphoblastic leukemia and synergistically works with dasatinib. Reviewed

    Morishita T, Hayakawa F, Sugimoto K, Iwase M, Yamamoto H, Hirano D, Kojima Y, Imoto N, Naoe T, Kiyoi H.

    Oncotarget.   Vol. 7   page: 56241   2016.7

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    Language:English   Publishing type:Research paper (scientific journal)  

  43. Fibroblast Growth Factor-2 facilitates the growth and chemo-resistance of leukemia cells in the bone marrow by modulating osteoblast functions. Reviewed

    Sugimoto K, Miyata Y, Nakayama T, Saito S, Suzuki R, Hayakawa F, Nishiwaki S, Mizuno H, Takeshita K, Kato H, Ueda R, Takami A, Naoe T.

    Scientific Reports   Vol. 6   page: 30779   2016.7

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    Language:English   Publishing type:Research paper (scientific journal)  

  44. PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation. Reviewed

    Inagaki Y, Hayakawa F, Hirano D, Kojima Y, Morishita T, Yasuda T, Naoe T, Kiyoi H.

    Biochem Biophys Res Commun.   Vol. 475 ( 2 ) page: 176   2016.5

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    Language:English   Publishing type:Research paper (scientific journal)  

  45. SPIB is a novel prognostic factor in diffuse large B-cell lymphoma that mediates apoptosis via the PI3K-AKT pathway. Reviewed

    Takagi Y, Shimada K, Shimada S, Sakamoto A, Naoe T, Nakamura S, Hayakawa F, Tomita A, Kiyoi H.

    Cancer Science   Vol. 107 ( 9 ) page: 1270   2016.4

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    Language:English   Publishing type:Research paper (scientific journal)  

  46. Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults. Reviewed

    Yasuda T, Tsuzuki S, Kawazu M, Hayakawa F, Kojima S, Ueno T, Imoto N, Kohsaka S, Kunita A, Doi K, Sakura T, Yujiri T, Kondo E, Fujimaki K, Ueda Y, Aoyama Y, Ohtake S, Takita J, Sai E, Taniwaki M, Kurokawa M, Morishita S, Fukayama M, Kiyoi H, Miyazaki Y, Naoe T, Mano H.

    Nature Genetics   Vol. 48 ( 5 ) page: 569   2016.3

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    Language:English   Publishing type:Research paper (scientific journal)  

  47. Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma. Reviewed

    Shimada K, Shimada S, Sugimoto K, Nakatochi M, Suguro M, Hirakawa A, Hocking TD, Takeuchi I, Tokunaga T, Takagi Y, Sakamoto A, Aoki T, Naoe T, Nakamura S, Hayakawa F, Seto M, Tomita A, Kiyoi H.

    Leukemia   Vol. 30 ( 7 ) page: 1568   2016.2

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    Language:English   Publishing type:Research paper (scientific journal)  

  48. Wnt signaling is associated with cell survival in the interaction between acute myeloid leukemia cells and stromal cells. Reviewed

    Niwa Y, Minami Y, Abe A, Hayakawa F, Yamada K, Naoe T.

    Leukemia & Lymphoma   Vol. 57 ( 9 ) page: 2192   2016.1

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    Language:English   Publishing type:Research paper (scientific journal)  

  49. B Cell Linker Protein (BLNK) Is a Selective Target of Repression by PAX5-PML Protein in the Differentiation Block That Leads to the Development of Acute Lymphoblastic Leukemia. Reviewed

    Imoto N, Hayakawa F, Kurahashi S, Morishita T, Kojima Y, Yasuda T, Sugimoto K, Tsuzuki S, Naoe T, Kiyoi H.

    Journal of Biological Chemistry   Vol. 291 ( 9 ) page: 4723   2016.1

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    Language:English   Publishing type:Research paper (scientific journal)  

  50. Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells. Reviewed International coauthorship

    Fukushima N, Minami Y, Kakiuchi S, et al.

    Cancer Science   Vol. 107   page: 1422   2016

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    Language:English   Publishing type:Research paper (scientific journal)  

  51. Adult acute lymphoblastic leukemia: current therapies and future perspectives Invited Reviewed

      Vol. 57   page: 230   2016

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    Authorship:Lead author, Last author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)  

  52. Fibroblast Growth Factor-2 facilitates the growth and chemo-resistance of leukemia cells in the bone marrow by modulating osteoblast functions. Reviewed

    Sugimoto K, Miyata Y, Nakayama T, et al.

    Scientific reports   Vol. 6   page: 30799   2016

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    Language:English   Publishing type:Research paper (scientific journal)  

  53. Discovery of a drug targeting microenvironmental support for lymphoma cells by screening using patient-derived xenograft cells Reviewed

    Keiki Sugimoto, Fumihiko Hayakawa, Satoko Shimada, Takanobu Morishita, Kazuyuki Shimada, Tomoya Katakai, Akihiro Tomita, Hitoshi Kiyoi, Tomoki Naoe

    Scientific reports   Vol. 5   page: 13054   2015.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/srep13054

  54. Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies. Reviewed

    Ogura M, Uchida T, Terui Y, Hayakawa F, Kobayashi Y, Taniwaki M, Takamatsu Y, Naoe T, Tobinai K, Munakata W, Yamauchi T, Kageyama A, Yuasa M, Motoyama M, Tsunoda T, Hatake K.

    Cancer Science   Vol. 106 ( 7 ) page: 896-901   2015.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.12683.

  55. Anti-cancer fatty-acid derivative induces autophagic cell death through modulation of PKM isoform expression profile mediated by bcr-abl in chronic myeloid leukemia. Reviewed

    Shinohara H, Taniguchi K, Kumazaki M, Yamada N, Ito Y, Otsuki Y, Uno B, Hayakawa F, Minami Y, Naoe T, Akao Y.

    Cancer Letter   Vol. 360 ( 1 ) page: 28-38   2015.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.canlet.2015.01.039.

  56. Adolescent and young adult世代の急性リンパ性白血病 Invited Reviewed

    早川文彦

    臨床血液   Vol. 56   page: 2032   2015

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    Authorship:Lead author, Last author, Corresponding author   Language:Japanese  

  57. Development of acute pure red cell aplasia after deferasirox administration in two cases of myelodysplastic syndrome. Reviewed

    Hayakawa F, Tomita A, Naoe T.

    Rinsho Ketsueki   Vol. 55 ( 4 ) page: 445-9   2014

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    Authorship:Lead author   Language:Japanese   Publishing type:Research paper (scientific journal)  

  58. Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group. Reviewed

    Hayakawa F, Sakura T, Yujiri T, Kondo E, Fujimaki K, Sasaki O, Miyatake J, Handa H, Ueda Y, Aoyama Y, Takada S, Tanaka Y, Usui N, Miyawaki S, Suenobu S, Horibe K, Kiyoi H, Ohnishi K, Miyazaki Y, Ohtake S, Kobayashi Y, Matsuo K, Naoe T

    Blood Cancer Journal   Vol. 4 ( e ) page: 252   2014

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  59. GATA2 zinc finger 2 mutation found in acute myeloid leukemia impairs myeloid differentiation. Reviewed

    Niimi K, Kiyoi H, Ishikawa Y, Hayakawa F, Kurahashi S, Kihara R, Tomita A, Naoe T.

    Leuk Res Rep   Vol. 2 ( 1 ) page: 21-5   2013

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  60. A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-addictive oncokinases. Reviewed

    Hayakawa F, Sugimoto K, Harada Y, Hashimoto N, Ohi N, Kurahashi S, Naoe T.

    Blood Cancer Journal   Vol. 3 ( e ) page: 166   2013

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  61. B cell receptor-ERK1/2 signal cancels PAX5-dependent repression of BLIMP1 through PAX5 phosphorylation: a mechanism of antigen-triggering plasma cell differentiation. Reviewed

    Yasuda T,Hayakawa F,Kurahashi S, Sugimoto K, Miyami Y, Tomita A, Naoe

    Journal of Immunology   Vol. 188 ( 12 ) page: 6127-34   2012

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  62. Missense mutations in PML-RARA critical for the lack of responsiveness to arsenic trioxide treatment. Reviewed

    Goto E, Tomita A, Hayakawa F, Atsumi A, Kiyoi H, Naoe T.

    Blood   Vol. 118 ( 6 ) page: 1600-9   2011

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  63. PAX5-PML acts as a dual dominant-negative form of both PAX5 and PML. Reviewed

    Kurahashi S, Hayakawa F, Miyata Y, Yasuda T, Minami Y, Tsuzuki S, Abe A, Naoe T.

    Oncogene   Vol. 30 ( 14 ) page: 1822-30   2011

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  64. The mTOR inhibitor, everolimus (RAD001), overcomes resistance to imatinib in quiescent Ph-positive acute lymphoblastic leukemia cells. Reviewed

    Kuwatsuka Y, Minami M, Minami Y, Sugimoto K, Hayakawa F, Miyata Y, Abe A, Goff DJ, Kiyoi H, Naoe T.

    Blood Cancer Journal   Vol. 1 ( e ) page: 17   2011

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  65. BCR-ABL-independent and RAS / MAPK pathway-dependent form of imatinib resistance in Ph-positive acute lymphoblastic leukemia cell line with activation of EphB4. Reviewed

    Suzuki M, Abe A, Imagama S, Nomura Y, Tanizaki R, Minami Y, Hayakawa F, Ito Y, Katsumi A, Yamamoto K, Emi N, Kiyoi H, Naoe T.

    Eur J Haematol.   Vol. 84 ( 3 ) page: 229-38   2010

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  66. Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy. Reviewed

    Abe A, Minami Y, Hayakawa F, Kitamura K, Nomura Y, Murata M, Katsumi A, Kiyoi H, Jamieson CH, Wang JY, Naoe T.

    Int J Hematol   Vol. 88 ( 5 ) page: 471-5   2008

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  67. Acetylation of PML is involved in histone deacetylase Inhibitor-mediated apoptosis. Reviewed

    Hayakawa F, Abe A, Kitabayashi I, Pandolfi PP, Naoe T.

    J Biol Chem.   Vol. 283 ( 36 ) page: 24420-5   2008

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  68. LRP16 is fused to RUNX1 in monocytic leukemia cell line with t(11;21)(q13;q22). Reviewed

    Imagama S, Abe A, Suzuki M, Hayakawa F, Katsumi A, Emi N, Kiyoi H, Naoe T.

    Eur J Haematol.   Vol. 79 ( 1 ) page: 25-31   2007

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  69. Response of SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) corepressors to mitogen-activated protein kinase kinase kinase cascades is determined by alternative mRNA splicing. Reviewed

    Jonas BA, Varlakhanova N, Hayakawa F, Goodson M, Privalsky ML.

    Mol Endocrinol   Vol. 21 ( 8 ) page: 1924-39   2007

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  70. Lyn is an important component of the signal transduction pathway specific to FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD. Reviewed

    Okamoto M*, Hayakawa F*, Miyata Y, Watamoto K, Emi N, Abe A, Kiyoi H, Towatari M, Naoe T

    Leukemia   Vol. 21 ( 3 ) page: 403-10   2007

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  71. SFK-STAT pathway: an alternative and important way to malignancies. Reviewed

    Hayakawa F, Naoe T

    Ann N Y Acad Sci   Vol. 1086 ( 1 ) page: 213-22   2006

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    Authorship:Lead author   Language:English  

  72. Establishment of a stroma-dependent human acute myelomonocytic leukemia cell line, NAMO-2, with FLT3 tandem duplication. Reviewed

    Abe A, Kiyoi H, Ninomiya M, Yamazaki T, Murase T, Ozeki K, Suzuki M, Hayakawa F, Katsumi A, Emi N, Naoe T

    Int J Hematol   Vol. 84 ( 4 ) page: 328 - 336   2006

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  73. Functional regulation of GATA-2 by acetylation. Reviewed

    Hayakawa F, Towatari M, Ozawa Y, Tomita A, Privalsky ML, Saito H.

    J Leukoc Biol   Vol. 75 ( 3 ) page: 529-40   2004

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  74. Phosphorylation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis. Reviewed

    Hayakawa F, Privalsky ML

    Cancer Cell   Vol. 5 ( 4 ) page: 389-401   2004

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  75. Life-threatening human parvovirus B19 infection transmitted by intravenous immune globulin. Reviewed

    Hayakawa F, Imada K, Towatari M, Saito H.

    Br J Haematol.   Vol. 118 ( 4 ) page: 1187-9   2002

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  76. Histone deacetylase 3 associates with and represses the transcription factor GATA-2. Reviewed

    Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, Tanimoto M, Saito H.

    Blood   Vol. 98 ( 7 ) page: 2116-23   2001

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  77. c-Myb acetylation at the carboxyl-terminal conserved domain by transcriptional co-activator p300. Reviewed

    Tomita A, Towatari M, Tsuzuki S, Hayakawa F, Kosugi H, Tamai K, Miyazaki T, Kinoshita T, Saito H.

    Oncogene   Vol. 19 ( 3 ) page: 444-51   2000

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  78. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Reviewed

    Hayakawa F, Towatari M, Kiyoi H, Tanimoto M, Kitamura T, Saito H, Naoe T

    Oncogene   Vol. 19 ( 5 ) page: 624-31   2000

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  79. Differential constitutive activation between STAT-related proteins and MAP kinase in primary acute myelogenous leukaemia. Reviewed

    Hayakawa F, Towatari M, Iida H, Wakao H, Kiyoi H, Naoe T, Saito H.

    Brithish Journal of Haematology   Vol. 101 ( 3 ) page: 521-8   1998

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

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Presentations 6

  1. Genetic abnormalities of AYA ALL and its treatment strategy by pediatric like protocols. Invited

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    Event date: 2016.10

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Country:Japan  

  2. Treatment of acute lymphoblastic leukemia in adolescent and young adult by pediatric protocols. Invited

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    Event date: 2016.10

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Country:Japan  

  3. New molecular targets of B-cell acute lymphoblastic leukemia Invited

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    Event date: 2016.10

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Country:Japan  

  4. Adolescent and young adult (AYA)世代の急性リンパ性白血病 Invited

    早川文彦

    第77回日本血液学会学術集会 

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    Event date: 2015.10

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Country:Japan  

  5. AYA ALL に対する小児プロトコールの有効性と認容の検討:JALSG ALL202-U 研究より Invited

    早川文彦

    第56回日本小児血液・がん学会学術集会シンポジウム 

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    Event date: 2014.11

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Country:Japan  

  6. Development of growth signal inhibitors for hematopoietic malignancies Invited

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    Event date: 2011.10

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Country:Japan  

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Research Project for Joint Research, Competitive Funding, etc. 8

  1. AYA世代および成人T細胞性急性リンパ性白血病の小児型治療適用における限界年齢と新規バイオマーカー探索に関する研究

    Grant number:20ck0106607h0001  2020.4

    革新的がん医療実用化研究事業 

    早川文彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\43500000

  2. AYA世代急性リンパ性白血病の小児型治療法および遺伝子パネル診断による層別化治療に関する研究 課題番号: 17ck0106331h0001

    Grant number:18ck0106331h0002  2017.4 - 2020.3

    革新的がん医療実用化研究事業 

    早川文彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\91500000

  3. AYA世代における急性リンパ性白血病の生物学的特性と小児型治療法に関する研究

    Grant number:16ck0106129h0003  2014.10 - 2017.3

    革新的がん医療実用化研究事業 

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\86903000

    小児型治療法によるAYA(思春期・若年成人)世代ALLの治療成績の向上、ゲノム解析による新たな予後因子の探索とそれに基づく層別化治療の確立を目的とし、AYA世代及び成人世代のALLに対する各種臨床研究の遂行と、患者検体を用いた網羅的な遺伝子解析を行う研究。

  4. フィラデルフィア染色体陽性急性リンパ性白血病に対するポナチニブを組み込んだ治療法の確立と分子基盤の解明

    2020.4 - 2023.3

    革新的がん医療実用化研究事業 

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    Authorship:Coinvestigator(s)  Grant type:Competitive

  5. 小児から成人をシームレスに対象とした B前駆細胞性急性リンパ性白血病に対する前方視的臨床試験による標準治療の開発研究

    Grant number:19ck0106505h0001  2019.4 - 2022.3

    革新的がん医療実用化研究事業 

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    Authorship:Coinvestigator(s)  Grant type:Competitive

  6. 成人B細胞性急性リンパ性白血病における融合遺伝子の情報に基づく分子生物学的な理解と新しい治療戦略の考案

    Grant number:17cm0106525h0002  2016.4 - 2018.3

    次世代がん医療創生研究事業 

    安田 貴彦

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\1040000 ( Direct Cost: \800000 、 Indirect Cost:\240000 )

  7. 造血器悪性腫瘍及び転移性がんで高頻度に異常を来している遺伝子を標的とした新たな治療法の開発に資する研究

    Grant number:201313007B  2013.4 - 2014.3

    厚生労働科学研究費補助金(厚生科研費) 

    北林 一生

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\6200000 ( Direct Cost: \4770000 、 Indirect Cost:\1430000 )

  8. 腫瘍抑制因子PMLのアセチル化による機能調節機構の解明とPML機能活性化による抗腫瘍療法

    2006.4 - 2007.3

    上原記念生命科学財団研究助成金 

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    Grant type:Competitive

    Grant amount:\2000000

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KAKENHI (Grants-in-Aid for Scientific Research) 8

  1. 分化誘導型アイソフォーム誘導療法によるMEF2D融合遺伝子陽性白血病治療

    Grant number:21K19505  2021.7 - 2024.3

    科学研究費助成事業  挑戦的研究(萌芽)

    早川 文彦

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    Authorship:Principal investigator 

    Grant amount:\6370000 ( Direct Cost: \4900000 、 Indirect Cost:\1470000 )

  2. ALLにおける新規高頻度融合遺伝子の白血病化メカニズムの解明 International coauthorship

    Grant number:18H02835  2018.4 - 2021.3

    科学研究費補助金  基盤研究(B)

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\16510000 ( Direct Cost: \12700000 、 Indirect Cost:\3810000 )

    本研究では、急性リンパ性白血病の新たな反復性遺伝子変異であるMEF2D融合遺伝子、ZNF384融合遺伝子の白血病化の機序を分子レベルで明らかにすることを目的に研究を行なっている。今年度はZNF384融合遺伝子を中心に解析し、以下のことを明らかにした。
    54例のB細胞性ALLの遺伝子発現プロファイルを解析し、ZNF384融合遺伝子陽性ALLで特異的に高発現しており、B細胞分化抑制に働くと予想される遺伝子を探索し、SALL4, ID2をZNF384融合蛋白の特異的転写標的候補として選別した。ALL細胞株にZNF384融合蛋白発現ベクターを導入すると野生型を導入した時よりも強くこれら遺伝子のmRNA発現が誘導された。SALL4, ID2のエンハンサー領域を用いたルシフェラーゼアッセイでZNF384融合蛋白は野生型より強い転写活性を示した。In vitroの結合実験でZNF384融合蛋白は野生型に比べて転写活性化補助因子p300との結合親和性が上昇していた。ZNF384融合蛋白の転写活性はp300を共発現することで増強し、その増強の程度は野生型ZNF384でみられるものより強かった。これらのことより、ZNF384融合蛋白はp300との結合親和性が高いことにより転写活性が異常に上昇し、SALL4, ID2などのB細胞分化抑制に働く遺伝子の発現を上昇させることでALL発症に寄与するというモデルを提唱し、一連の結果をFEBS letter誌に報告した。
    ZNF384融合遺伝子に関する研究は次年度研究論文投稿の予定であったが、計画の進捗が早く、また雑誌投稿後のアクセプトも早く、すでに論文発表を終えることができた。
    次年度はMEF2D融合遺伝子に関しては融合蛋白が高発現することが白血病化に重要であることを発見したことを踏まえ、この蛋白の減少を誘導する薬剤の白血病治療薬としての可能性を検討する。ZNF384融合遺伝子に関してはEP300, SYNRG以外の融合パートナーとの融合遺伝子に関しても検討を行う。

  3. Screening of therapeutic agent for Ph-positive ALL using patient-derived xenograft cells

    Grant number:15K09472  2015.4 - 2018.3

    Grant-in-Aid for Scientific Research(C)   Grant-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research(C)

    Fumihiko Hayakawa

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    We developed a high-throughput drug screening system using PDX cells and performed drug screening using the PDX cells of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). We performed a screening of 3440 compounds using leukemia cells from the PDX mice (PDX-cell screening). The profiles of drugs selected by PDX-cell screening were markedly different from those by screening using the Ph+ ALL cell line. We found that verteporfin, an FDA-approved drug, exhibited strong PDX cell-specific cytotoxicity. Although verteporfin is a photosensitizer activated by photoirradiation, its cytotoxic effects were mediated by the light-independent production of reactive oxygen species; therefore, its anti-leukemic effects were also exerted in vivo without photoirradiation. Furthermore, it exhibited synergistic effects with dasatinib, an ABL kinase inhibitor. These results indicated the potential of verteporfin as a new anti-leukemic reagent.

  4. 創薬に向けた白血病のトランスレーショナルリサーチ

    2013.4 - 2016.3

    科学研究費補助金  基盤研究(B)

    直江 知樹

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    がんにおけるドライバー変異を標的に薬剤が開発されてきたが、標的分子の変異やバイパスシグナルの活性化など、耐性獲得や抵抗性が問題となっている。本研究では耐性変異にも感受性のあるチロシンキナーゼ阻害剤、活性化変異チロシンキナーゼの下流で働く共通分子を標的とした薬剤、代謝を標的とした画期的な抗がん剤についての基礎研究を行った。その結果、点変異によって既存の阻害剤に耐性を示すFLT3分子にも感受性のある阻害剤、STAT3/5の活性を阻害する新規化合物、ならびにCMLに有効な中鎖脂肪酸誘導体を得ることができた。

  5. 形質細胞分化運命決定におけるMAPKシグナルの役割とその破綻によるリンパ腫発症

    2013.4 - 2015.3

    科学研究費補助金  新学術領域研究

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    Authorship:Principal investigator 

    B細胞の終末分化である形質細胞分化は、胚中心B細胞において抗原とB cell receptor (BCR)の遭遇を契機として、そこまでのB細胞分化を牽引してきたPAX5とその後の形質細胞分化を担うBLIMP1が入れ替わる事により開始される。本研究はこの分子的な機序を明らかにすることで、成熟B細胞から形質細胞への分化という運命決定におけるBCRシグナルの役割を明らかにする事を目的として行われた。
    BCRシグナルの重要な構成キナーゼであるSyk, Btk, Akt, によるPAX5のリン酸化をin vitroで検討しSykがPAX5をチロシンリン酸化する事を発見し、そのリン酸化部位を同定した。293T細胞内でSykとPAX5の共発現はPAX5チロシンリン酸化を誘導した。PAX5はNFκBによるBLIMP1発現誘導を抑制する作用があるが、レポータージーンアッセイではSyk共発現によりPAX5によるBLIMP1発現抑制が解除され、リン酸化チロシン変異PAX5を用いるとこの解除が起こらなかった。更に胚中心B細胞細胞株であるRamos細胞ではBCR刺激がPAX5チロシンリン酸化を介してBLIMP1の発現を上昇させていた。
    我々は以前にMAPキナーゼによるPAX5のセリンリン酸化が同様の効果を示すことを報告しているが、今回発見したチロシンリン酸化とセリンリン酸化は協調的に作用してPAX5によるBLIMP1発現抑制の解除に作用していることをレポータージーンアッセイとRamos細胞のBCRを刺激することの両方のシステムで確認した。これらのことから、BCRシグナルにおいてSykとMAPキナーゼが協調的に働き、PAX5の機能を抑制する事でBLIMP1の発現を誘導し、形質細胞分化の契機となっている事が示唆された。

  6. 悪性リンパ腫における微小環境依存性と治療開発に関する研究

    2013.4 - 2015.3

    科学研究費補助金  研究成果公開促進費 (研究成果公開発表)

    直江 知樹

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    Authorship:Coinvestigator(s) 

    抗がん剤開発においては、細胞株と実際の腫瘍のギャップを埋めるスクリーニング系の開発が大きな課題となっている。本研究ではヒトプライマリリンパ腫細胞を免疫不全マウスに移植しPDXマウスを作成し、リンパ腫ニッチを探索した。PDXマウスから取り出したPDX細胞は細胞株に比べて、プライマリ腫瘍細胞の形質が高度に保存された細胞で、これの体外培養法を確立し、それを用いたハイスループットな薬剤スクリーニング方法を確立した。スクリーニングで選別された薬剤を解析することで、リンパ腫細胞は間質細胞から還元型グルタチオンの供給を受け酸化ストレスから保護されているという新しい腫瘍生存機序が発見された。

  7. PML の SUMO E3リガーゼ同定によるPML NB形成機構解明 

    2008.4 - 2011.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

    腫瘍抑制因子PMLはその機能発現においてSUMO化という翻訳後修飾を介してPML nuclear body (PML NB)と呼ばれる核内構造物を形成する事が必要である。SUMO化の調節にはSUMO E3 リガーゼと呼ばれる酵素が重要である事がいくつかの蛋白で示されているが、PMLのSUMO E3 リガーゼはまだ同定されていない。本研究では、PMLの SUMO化にはPML自身が必要であるであるという申請者の発見に基づき、これを詳細に解析し、またPMLによりSUMO化を調節される新たな蛋白を同定し、PML NB構成の機構ならびにPML SUMO化の意義を明らかにする事を目的としている。本研究によりPMLの機能発現調節の機構が明らかにされ、PMLを利用した抗腫瘍療法の開発に役立つと考えられる。

  8. 白血病関連遺伝子産物PMLのアセチル化の意義

    2006.4 - 2008.3

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

    本研究の目的はPML機能のアセチル化による調節の機構解明、及びアセチル化を介したPML機能増強によるAPL細胞のアポトーシス誘導にある。我々はこれまでに試験管内でPMLがヒストンアセチル化酵素であるp300、GCN5によりアセチル化される事を証明しそのアセチル化部位を同定した。細胞内でもPMLがアセチル化されており、それは既知のヒストン脱アセチル化酵素阻害剤であるトリコスタチンA(TSA)の刺激により増強される事も見いだした。更に細胞内ではPMLのアセチル化がPMLのSUM0化を増強する事を発見した。PMLをsiRNAによりノックダウンしたHeLa細胞、あるいはPMLノックアウトマウスより作製したMEF細胞を用いる事により、PMLアセチル化により誘導されるPML SIM0化がTSAによる腫瘍細胞のアポトーシスのメガニズムとして重要である事が示された。我々の成果は腫瘍抑制因子PMLの新規翻訳後修飾としてアセチル化を見いだす事によりその機能調節に対する理解を深めると供に、有用な抗がん剤候補と考えられながらその作用機序の多くが不明であるヒストン脱アセチル化酵素阻害剤の作用機序の一部を解明する事に繋がるものである。

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Teaching Experience (On-campus) 9

  1. Laboratory Molecular Genetics Practice

    2020

  2. Molecular Pathophysiology

    2020

  3. Laboratory Hematology Practice C

    2020

  4. Laboratory Hematology PracticeA

    2020

  5. Clinical Medicine II

    2020

  6. Medical Technology Special Lecture I

    2020

  7. Laboratory Hematology II

    2020

  8. Laboratory Hematology I

    2020

  9. General Clinical Pathology Exercise

    2020

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