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Reprogramming technology revealed the genetic and functional diversity present in an individual myelodysplastic syndrome patient

Research Project

Project/Area Number 16K09847
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Chonabayashi Kazuhisa  京都大学, iPS細胞研究所, 特定研究員 (00646010)

Research Collaborator Yoshida Yoshinori  
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords骨髄異形成症候群 / 二次性急性骨髄性白血病 / リプログラミング / iPS細胞 / 腫瘍内多様性 / 新規治療薬
Outline of Final Research Achievements

We successfully generated multiple iPS cell lines from abnormal clones of patients with myelodysplastic syndromes or secondary AML (MDS/sAML) evolved from MDS. Hematopoietic progenitor cells (HPCs) differentiated from MDS-derived MDS-iPS cell lines showed decreased colony formation, whereas HPCs differentiated from sAML-derived MDS-iPS cell lines showed increased colony formation, compared with isogenic normal iPS cell lines, and induced lethal AML in transplanted immunodeficient mice. Next, we performed whole-exome analysis to find that some of the somatic mutations detected in bulk cells of MDS/sAML patients are shared in MDS-iPS cell lines but not in isogenic normal iPS cell lines. Furthermore, we performed coprehensive gene expression analysis in hematopoietic progenitor cells differentiated from MDS-iPS cell lines and isogenic normal iPS cell lines, identifying disease-specific expression change.

Academic Significance and Societal Importance of the Research Achievements

予後不良のクローン性造血障害であるMDS/sAMLには病態を再現し解析するモデルが殆どなく、治療法の開発を可能にするツールが殆どないのが現状である。我々は患者から樹立した複数のMDS-iPS細胞株の網羅的ゲノム解析と、MDS-iPS細胞から再誘導された造血前駆細胞の分化能・造腫瘍能などの機能解析を組み合わせることにより、MDS/sAMLの腫瘍内多様性及び発症・進展機構を明らかした。

Report

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

    (8 results)

All 2019 2018 2017 2016 Other

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

  • [Journal Article] Escape hematopoiesis by HLA-B5401-lacking hematopoietic stem progenitor cells in men with acquired aplastic anemia.2019

    • Author(s)
      Mahmoud I. Elbadry、Mizumaki Hiroki、Hosokawa Kohei、J. Luis Espinoza、Nakagawa Noriharu、Chonabayashi Kazuhisa、Yoshida Yoshinori、Katagiri Takamasa、Hosomichi Kazuyoshi、Zaimoku Yoshitaka、Imi Tatsuya、Mai Anh Thi Nguyen、Fujii Youichi、Tajima Atsushi、Ogawa Seishi、Takenaka Katsuto、Akashi Koichi、Nakao Shinji
    • Journal Title

      Haematologica

      Volume: 印刷中 Issue: 10 Pages: 210856-210856

    • DOI

      10.3324/haematol.2018.210856

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack2018

    • Author(s)
      Espinoza J. Luis、Elbadry Mahmoud I.、Chonabayashi Kazuhisa、Yoshida Yoshinori、Katagiri Takamasa、Harada Kenichi、Nakagawa Noriharu、Zaimoku Yoshitaka、Imi Tatsuya、Hassanein Hassan A.、Khalifa A. Noreldin Amal、Takenaka Katsuto、Akashi Koichi、Hamana Hiroshi、Kishi Hiroyuki、Akatsuka Yoshiki、Nakao Shinji
    • Journal Title

      Blood Adv

      Volume: 2 Issue: 4 Pages: 390-400

    • DOI

      10.1182/bloodadvances.2017013342

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reprogramming technology reveals genetic and functional diversity of subclones in myelodysplastic syndromes2017

    • Author(s)
      Chonabayashi K, Yoshida Y, Takaori-Kondo A.
    • Journal Title

      Rinsho Ketsueki

      Volume: 58 Issue: 7 Pages: 787-791

    • DOI

      10.11406/rinketsu.58.787

    • NAID

      130005907578

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] iPS technology revealed the genetic and functional diversity present in a myelodysplastic syndrome patient.2018

    • Author(s)
      Kazuhisa Chonabayashi, Akira Watanabe, Akifumi Takaori-Kondo, and Yoshinori Yoshida
    • Organizer
      International Society for Stem Cell Research Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS technology revealed the genetic and functional diversity present in a myelodysplastic syndrome patient.2018

    • Author(s)
      Kazuhisa Chonabayashi, Akira Watanabe, Akifumi Takaori-Kondo, and Yoshinori Yoshida
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] iPS technology revealed the genetic and functional diversity present in a secondary AML patient2016

    • Author(s)
      Kazuhisa Chonabayashi, Masahiro Kawahara, Akira Watanabe, Masahiro Nakamura, Masatoshi Nishizawa, Akifumi Takaori-Kondo, Shinya Yamanaka, Yoshinori Yoshida.
    • Organizer
      The 58th Annual Meeting of the American Society of Hematology.
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 吉田研究室

    • Related Report
      2017 Research-status Report
  • [Remarks] 吉田研究室

    • Related Report
      2016 Research-status Report

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

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