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Analysis of molecular mechanisms in RUNX1-EVI1-type leukemia

Research Project

Project/Area Number 16K09858
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionDokkyo Medical University

Principal Investigator

Mitani Kinuko  獨協医科大学, 医学部, 教授 (50251244)

Co-Investigator(Kenkyū-buntansha) 市川 幹  獨協医科大学, 医学部, 准教授 (60463840)
佐々木 光  獨協医科大学, 医学部, 准教授 (60282638)
中村 由香  獨協医科大学, 医学部, 講師 (80364595)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsRUNX1-EVI1 / t(3;21) / 急性巨核芽球性白血病 / SKP2 / ヒストン脱アセチル化酵素阻害剤 / 血小板増多 / 骨髄異形成 / CD41 / 中心体 / 内科 / 癌 / 遺伝子 / 発現制御
Outline of Final Research Achievements

RUNX1-EVI1 is a chimeric transcription factor generated by t(3;21) and causes the development of acute megakaryoblastic leukemia or transformation of chronic myelocytic leukemia and myelodysplastic syndrome. By using transplantation experiments, we created RUNX1-EVI1-type model mice. A part of the mice developed acute megakaryoblastic leukemia within eight months, which was considered to mimic human leukemia. Passage of the leukemic cells was possible through the second and third transplantation.

Academic Significance and Societal Importance of the Research Achievements

RUNX1-EVI1型白血病は極めて予後が不良であり、化学療法のみでは治癒は困難である。今回作製されたモデルマウスを解析することにより、予後不良の白血病の発症機構が詳細に解明されることが期待される。また、これらの知見を基にして、今後新規の分子標的療法の開発が可能となる。RUNX1-EVI1はキメラ型転写因子であり、すでに臨床応用されているヒストン脱アセチル化酵素阻害剤の効果も検証する予定である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Invited: 2 results)

  • [Journal Article] RUNX1-EVI1 induces dysplastic hematopoiesis and acute leukemia of the megakaryocytic lineage in mice.2018

    • Author(s)
      Nakamura Y, Ichikawa M, Oda H, Yamazaki I, Sasaki K, Mitani K.
    • Journal Title

      Leukemia Res

      Volume: 74 Pages: 14-20

    • DOI

      10.1016/j.leukres.2018.09.015

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Validation of the revised International Prognostic Scoring System in patients with myelodysplastic syndrome in Japan: results from a prospective multicenter registry2017

    • Author(s)
      Kawabata H, Tohyama K, Matsuda A, Araseki K, Hata T, Suzuki T, Kayano H, Shimbo K, Zaike Y, Usuki K, Chiba S, Ishikawa T, Arima N, Nogawa M, Ohta A, Miyazaki Y, Mitani K, Ozawa K, Arai S, Kurokawa M, Takaori-Kondo A
    • Journal Title

      International Journal of Hematology

      Volume: 106 Issue: 3 Pages: 375-384

    • DOI

      10.1007/s12185-017-2250-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Somatic mosaicism in chronic myeloid leukemia in remission.2016

    • Author(s)
      Mitani K, Nagata Y, Sasaki K, Yoshida K, Chiba K, Tanaka H, Shiraishi Y, Miyano S, Makishima H, Nakamura Y, Nakamura Y, Ichikawa M, Ogawa S.
    • Journal Title

      Blood.

      Volume: 128 Issue: 24 Pages: 2863-2866

    • DOI

      10.1182/blood-2016-06-723494

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Chronic myelogenous leukemia in chronic phase transforming into acute leukemia under treatment with dasatinib 4 months after diagnosis.2016

    • Author(s)
      Nakamura Y, Tokita T, Nagasawa F, Takahashi W, Nakamura Y, Sasaki K, Ichikawa M, Mitani K.
    • Journal Title

      Int J Hematol.

      Volume: 103 Issue: 3 Pages: 348-353

    • DOI

      10.1007/s12185-015-1909-7

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] AMLの分子標的療法と分子病態2018

    • Author(s)
      三谷絹子
    • Organizer
      第115回日本内科学会総会・講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] RUNX1-EVI1 キメラ遺伝子による白血病モデルマウスの解析.2017

    • Author(s)
      中村由香、市川幹、小田秀明、山崎家春、佐々木光、三谷絹子
    • Organizer
      第54回日本臨床分子医学会学術集会
    • Related Report
      2017 Research-status Report 2016 Research-status Report
  • [Presentation] Presidential Lecture Leukemogenesis by RUNX1-EVI1 and afterward stories ~a message to young doctors and researchers~.2016

    • Author(s)
      Kinuko Mitani
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] RUNX1-EVI1 fusion gene induces an acute megakaryoblastic leukemia in mice.2016

    • Author(s)
      Yuka Nakamura, Motoshi Ichikawa, Ieharu Yamazaki, Ko Sasaki, Kinuko Mitani
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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