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Investigating the role and therapeutic targets of cellular senescence in the development and transformation of myelodysplastic syndrome

Research Project

Project/Area Number 17H06632
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

Uni Masahiro  東京大学, 医学部附属病院, 特任臨床医 (20802359)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords骨髄異形成症候群
Outline of Final Research Achievements

With our Asxl1 heterozygous mutant knock-in mice, which recapitulates human myelodysplastic syndrome (MDS) well, we confirmed high expression of genes associated with cellular senescence, and also validated these in protein level. We further indicated the contribution of cellular senescence-related inflammatory cytokine secretion in the development of secondary leukemia from MDS. Finally, we intercrossed MDS model mice above with p16 knock-out mice, and showed restoration of phenotypes of human MDS in vivo.

Academic Significance and Societal Importance of the Research Achievements

骨髄異型性症候群(MDS)は高齢者の高頻度に認められる予後不良の造血器腫瘍であるのみならず、急性骨髄性白血病への高頻度の進展も知られているが、MDSに対する現行の治療には根治的治療は含まれず、根本的な解決を得たとは言い難い。MDSの病態を捉え、それに適した治療法を開発することは喫緊の課題と言って良く、本研究はその治療標的の一端として細胞老化に可能性があることを見出した。これを標的とした治療がMDSに如何なる影響を及ぼすかについては、引き続き研究が必要とされる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (7 results)

All 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Modeling ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant PRC1-mediated histone modification2018

    • Author(s)
      Uni Masahiro、Masamoto Yosuke、Sato Tomohiko、Kamikubo Yasuhiko、Arai Shunya、Hara Eiji、Kurokawa Mineo
    • Journal Title

      Leukemia

      Volume: 33 Issue: 1 Pages: 191-204

    • DOI

      10.1038/s41375-018-0198-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of ASXL1 mutation in impaired hematopoiesis and cellular senescence2018

    • Author(s)
      Uni Masahiro、Kurokawa Mineo
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 96 Pages: 36828-36829

    • DOI

      10.18632/oncotarget.26423

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant histone modification2018

    • Author(s)
      Masahiro Uni, Yosuke Masamoto, Tomohiko Sato, Yasuhiko Kamikubo, Shunya Arai, Eiji Hara and Mineo Kurokawa
    • Organizer
      The 16th Stem Cell Research Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] Modeling ASXL1 Mutation Revealed Myelodysplasia Caused By Derepression of p16Ink4a through Aberrant PRC1-Mediated Histone Modification2018

    • Author(s)
      Masahiro Uni, Yosuke Masamoto, Tomohiko Sato, Shunya Arai, Eiji Hara and Mineo Kurokawa
    • Organizer
      The 22nd Hematological malignancy meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] ASXL1 mutation induces MDS with derepression of p16Ink4a via aberrant histone modification by PRC1.2017

    • Author(s)
      Masahiro Uni, Yosuke Masamoto, Tomohiko Sato, Shunya Arai and Mineo Kurokawa
    • Organizer
      The 76th Annual Meeting of the Japanese Society of Hematology
    • Related Report
      2017 Annual Research Report
  • [Presentation] ASXL1 mutation induces MDS with derepression of p16Ink4a via aberrant histone modification by PRC1.2017

    • Author(s)
      Masahiro Uni, Yosuke Masamoto, Tomohiko Sato, Shunya Arai and Mineo Kurokawa
    • Organizer
      The 79th Annual Meeting of the Japanese Society of Hematology
    • Related Report
      2017 Annual Research Report
  • [Presentation] Modeling ASXL1 Mutation Revealed Myelodysplasia Caused By Derepression of p16Ink4a through Aberrant PRC1-Mediated Histone Modification2017

    • Author(s)
      Masahiro Uni, Yosuke Masamoto, Tomohiko Sato, Shunya Arai, Eiji Hara and Mineo Kurokawa
    • Organizer
      The 59th ASH Annual Meeting and Exposition
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-08-25   Modified: 2020-03-30  

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