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Molecular mechanism of MLL mutant-induced MDS

Research Project

Project/Area Number 23591367
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionChiba University

Principal Investigator

SASHIDA Goro  千葉大学, 医学(系)研究科(研究院), 助教 (70349447)

Co-Investigator(Renkei-kenkyūsha) IWAMA Atsushi  千葉大学, 大学院医学研究院, 教授 (70244126)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsMLL-PTD / RUNX1 / 骨髄異形成症候群 / 急性骨髄性白血病 / 国際情報交換 / MDS / エピジェネティクス / 造血幹細胞
Research Abstract

Given that MLL-PTD regulates the expression of RUNX1 mutants at protein level, we generated a novel MDS/AML mouse model by utilizing MLL-PTD knock-in mouse and Runx1 heterozygous mouse or RUNX1 mutants. We also demonstrated how MLL-PTD and RUNX1 mutants collaborated to induce the development of MDS and promote AML following MDS.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (13 results)

All 2013 2012 2011

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (8 results)

  • [Journal Article] Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders2013

    • Author(s)
      Muto T, Sashida G, Oshima M, et al.
    • Journal Title

      J Exp Med

      Volume: 18 Pages: 2627-39

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells.2012

    • Author(s)
      Zhang Y, Yan X, Sashida G et al.
    • Journal Title

      Blood

      Volume: 120 Issue: 5 Pages: 1118-29

    • DOI

      10.1182/blood-2012-02-412379

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ezh2 augments leukemogenecity by reinforcing differentiation blockage in acute myeloid leukemia2012

    • Author(s)
      Tanaka S
    • Journal Title

      Blood

      Volume: 120 Issue: 5 Pages: 1107-17

    • DOI

      10.1182/blood-2011-11-394932

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic regulation of hematopoiesis.2012

    • Author(s)
      Sashida G, Iwama A.
    • Journal Title

      Int J Hematol.

      Volume: 96 Issue: 4 Pages: 405-12

    • DOI

      10.1007/s12185-012-1183-x

    • NAID

      10031126731

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The ability of MLL to bind RUNX1 and methylate...2011

    • Author(s)
      Huang G, Zhao X, Wang L, et al.
    • Journal Title

      Blood

      Volume: 118 Pages: 6544-6552

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Modeling and Targeting MLL-PTD/RUNX1 Related MDS/AML In Mouse2013

    • Author(s)
      Yue Zhang, Xiaomei Yan, Aili Chen, Goro Sashida, Zhijian Xiao, and Gang Huang
    • Organizer
      アメリカ血液学会
    • Place of Presentation
      ニューオリンズ、米国(Blood 2013 122:2746)
    • Year and Date
      2013-12-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Modeling and Targeting MLL-PTD/RUNX1 Related MDS/AML In Mouse2013

    • Author(s)
      Zhang Y, Yan X, Chen A, Sashida G, et al.
    • Organizer
      アメリカ血液学会
    • Place of Presentation
      ニューオリンズ(アメリカ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Ezh2 Loss Accelerates JAK2V617F-Driven Primary Myelofibrosis2013

    • Author(s)
      Tomioka T, Sashida G, et al.
    • Organizer
      アメリカ血液学会
    • Place of Presentation
      ニューオリンズ(アメリカ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Modeling MLL-PTD Related Myelodysplastic Syndromes in Mouse2012

    • Author(s)
      Xiaomei Yan, Yue Zhang, Goro Sashida, Aili Chen, Xinghui Zhao, Susan Whitman, Qianfei Wang, Michael A. Caligiuri, Zhijian Xiao, and Gang Huang
    • Organizer
      アメリカ血液学会
    • Place of Presentation
      アトランタ、米国(Blood 2012; 120: 2811)
    • Year and Date
      2012-12-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Stress Hematopoiesis Reveals Abnormal Control of Self-Renewal, Lineage-Bias and Myeloid Differentiation in Mll Partial Tandem Duplication (Mll-PTD) Hematopoietic Stem/Progenitor Cells2012

    • Author(s)
      Yue Zhang, Xiaomei Yan, Goro Sashida, Xinghui Zhao, Yalan Rao, Susumu Goyama, Susan Whitman, Nicholas Zorko, Kelsie M. Bernot, Rajeana M. Conway, David Witte, Qianfei Wang, Daniel G Tenen, Zhijian Xiao, Guido Marcucci, James C. Mulloy, H. Leighton Grimes, Michael A. Caligiuri, and Gang Huang
    • Organizer
      アメリカ血液学会
    • Place of Presentation
      アトランタ、米国(Blood 2012; 120: 3501)
    • Year and Date
      2012-12-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Modeling MLL-PTD Related Myelodysplastic Syndromes in Mouse2012

    • Author(s)
      Yan X, Zhang Y, Sashida G, et al.
    • Organizer
      American Society of Hematology
    • Place of Presentation
      米国アトランタ
    • Related Report
      2012 Research-status Report
  • [Presentation] Loss of Ezh2 Promotes the Development of Mutant-RUNX1 Induced MDS2012

    • Author(s)
      Sashida G, Tanaka S, et al.
    • Organizer
      American Society of Hematology
    • Place of Presentation
      米国アトランタ
    • Related Report
      2012 Research-status Report
  • [Presentation] MLL-PTD Causes Hypomorph Condition of CBF Complex (RUNX1/CBFβ) and Predisposes the Abnormal Hematopoietic Stem and Progenitor Cells (HSPCs) to Clonal Expansion2011

    • Author(s)
      Yue Zhang, Xiaomei Yan, Goro Sashida, Xinghui Zhao, Yalan Rao, Susumu Goyama, Susan P. Whitman, Nicholas Zorko, Kelsie M. Bernot, David Witte, Qian-fei Wang, Daniel G. Tenen, Zhijian Xiao, Guido Marcucci, James C. Mulloy, Michael A Caligiuri, and Gang Huang
    • Organizer
      アメリカ血液学会
    • Place of Presentation
      サンディエゴ、米国(Blood 2011; 118: 2801)
    • Year and Date
      2011-12-10
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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