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Establishment of new targeted therapy against acute blastic transformation of chronic myeloid leukemia

Research Project

Project/Area Number 24790962
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

TOMOHIKO Sato  東京大学, 医学部附属病院, 助教 (90553694)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords白血病幹細胞
Research Abstract

Introduction of CML into Evi1-IRES-GFP knock-in mice, a versatile HSC-reporter strain, enables us to separate Evi1-high CML cells from the individual. Evi1-IRES-GFP allele models of CML in chronic phase (CML-CP) revealed that Evi1 is predominantly enriched in the stem cell fraction and associated with an enhanced proliferative as well as a leukemia-initiating capacity and that Evi1-high CML-CP cells exhibit resistance to TKIs. Overexpressing BCR-ABL and NUP98-HOXA9 in Evi1-IRES-GFP knock-in mice to model CML in blast crisis (CML-BC), in which Evi1-high cells turned to be a major population as opposed to a minor population in CML-CP models, showed that Evi1-high CML-BC cells have a greater potential to recapitulate the disease and appear resistant to TKIs. Given that Evi1 heterozygosity ameliorates CML-CP and CML-BC development and that the combination of Evi1 and BCR-ABL causes acute myeloid leukemia resembling CML-BC, Evi1 could regulate CML development as a potent driver.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (8 results)

All 2014 2012 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.2014

    • Author(s)
      Sato T, Goyama S, Kataoka K, Nasu R, Tsuruta-Kishino T, Kagoya Y, Nukina A, Kumagai K, Kubota N, Nakagawa M, Arai S, Yoshimi A, Honda H, Kadowaki T, Kurokawa M.
    • Journal Title

      Oncogene

      Volume: 33 Issue: 42 Pages: 5028-5038

    • DOI

      10.1038/onc.2014.108

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evi1 Defines Leukemia-initiating Capacity and Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia2014

    • Author(s)
      Tomohiko Sato, Susumu Goyama, Keisuke Kataoka, Ryo Nasu, Takako Tsuruta-Kishino, Yuki Kagoya, Arika Nukina, Katsuyoshi Kumagai, Naoto Kubota, Masahiro Nakagawa, Shunya Arai, Akihide Yoshimi, Hiroaki Honda, Takashi Kadowaki and Mineo Kurokawa
    • Journal Title

      Oncogene

      Volume: xxx

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Evi1 Defines Leukemia-initiating Capacity and Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia2014

    • Author(s)
      Tomohiko Sato, Susumu Goyama, Keisuke Kataoka, Ryo Nasu, Takako Tsuruta-Kishino, Yuki Kagoya, Arika Nukina, Katsuyoshi Kumagai, Naoto Kubota, Masahiro Nakagawa, Shunya Arai, Akihide Yoshimi, Hiroaki Honda, Takashi Kadowaki and Mineo Kurokawa
    • Organizer
      AACR 2014 annual meeting
    • Place of Presentation
      San Diego, CA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Regulation of Chronic Myeloid Leukemia Stem Cells by Leukemia Oncogene Evi12012

    • Author(s)
      Sato T, Goyama S, Kataoka K, Nasu R, Honda H, Nakagawa M, Kumano K and Kurokawa M
    • Organizer
      第10回幹細胞シンポジウム
    • Place of Presentation
      淡路夢舞台
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of Chronic Myeloid Leukemia Stem Cells by Leukemia Oncogene Evi12012

    • Author(s)
      Sato T, Goyama S, Kataoka K, Tsuruta T, Nasu R, Nakagawa M, Kumano K and Kurokawa M
    • Organizer
      The 17th Congress of European Hematology Association
    • Place of Presentation
      RAI Amsterdam, Netherlands
    • Related Report
      2013 Final Research Report
  • [Presentation] 難治性白血病関連因子Evi1 による慢性骨髄性白血病幹細胞制御2012

    • Author(s)
      佐藤 智彦, 黒川 峰夫
    • Organizer
      第16回日本がん分子標的治療学会学術集会
    • Place of Presentation
      小倉市西日本総合展示場
    • Related Report
      2013 Final Research Report
  • [Presentation] REGULATION OF CHRONIC MYELOID LEUKEMIA STEM CELLS BY LEUKEMIA ONCOGENE EVI12012

    • Author(s)
      Tomohiko Sato, Susumu Goyama, Keisuke Kataoka, Takako Tsuruta, Ryo Nasu, Masahiro Nakagawa, Keiki Kumano and Mineo Kurokawa
    • Organizer
      17th Congress of European Hematology Association
    • Place of Presentation
      Amsterdam, Netherlands
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.u-tokyo-hemat.com/

    • Related Report
      2013 Final Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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