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In vivo stem cell tracking of myeloproliferative disease and identification of novel molecular targets

Research Project

Project/Area Number 26860721
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

SATO TOMOHIKO  東京大学, 医学部附属病院, 研究員 (90553694)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords白血病幹細胞 / 白血病モデルマウス / 造血幹細胞 / 遺伝子変異 / 慢性骨髄単球性白血病 / 遺伝子異常 / 骨髄性白血病
Outline of Final Research Achievements

In CMML-developed Evi1-GFP;Kras-mutant mice, no GFP(Evi1)-positive leukemia cells were detected.
Even after 20-month observation, Evi1-GFP;ASXL-mutant knock-in mice looked healthy with no apparent signs of acute myeloid leukemia or myelodysplastic syndrome. ASXL-mutant knock-in BM cells showed a skewed differentiation to myeloid lineage. ASXL-mutant knock-in BM cells had 2.3-times higher hematopoietic colony formation capacity and higher replating capacity up to five times. These cells had a similar BM reconstituting capacity to wild type BM cells (eight-month observation). Retroviral CML induction to ASXL-mutant knock-in BM cells showed no acceleration of CML development, but recipients with IDH1-mutant transduced ASXL-mutant knock-in BM cells had leukemia development with 10-month duration while ASXL-wild counterparts showed no leukemia so far.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (2 results)

All 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (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
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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
    • Place of Presentation
      San Diego Convention Center
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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