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Integrative understanding of the functional role of DNA demethylation-associated molecule in the process of leukemic initiation

Research Project

Project/Area Number 18K08352
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionMie University

Principal Investigator

Ono Ryoichi  三重大学, 医学系研究科, 准教授 (40422414)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords造血器腫瘍 / 白血病 / DNAメチル化
Outline of Final Research Achievements

In this study, we focused on the epigenetic mechanism controlling gene expression, which has been reported to play an important role in the molecular mechanism of oncogenesis including leukemogenesis, and performed various molecular biological analyses using several leukemia mouse model systems. Consequently, it was suggested that ablation of one of DNA demethylation-associated molecules contributed to the development of acute promyelocytic leukemia in an in vitro model system. On the other hand, in acute myeloid leukemia, ablation of the above molecule did not affect the main molecular pathogenesis. It is considered that we have found a part of the complexity of the functional aspects of epigenetic regulatory molecules, and we are planing to do further detailed analysis.

Academic Significance and Societal Importance of the Research Achievements

白血病は、血液の「がん」であり、強力な治療法が開発された今日においても、根治が困難なケースが存在する。そうした場合の切り札の一つが、白血病細胞に非常に特徴的な性質を攻撃する分子標的療法である。本研究では、近年白血病の発症に重要な役割を担うことが判明してきた、ゲノムDNAの化学的修飾の一つ、メチル化に関連した解析を行い、ある種の白血病では、そうしたメチル化を取り除く分子が白血病発症に一定の寄与をしているようであるが、別のタイプではしてないと考えられ、この種の分子を分子標的とするには、さらなる詳細な解析を要すると考えられた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (1 results) Remarks (3 results)

  • [Journal Article] Tet1 is not required for myeloid leukemogenesis by MLL-ENL in novel mouse models.2021

    • Author(s)
      Ono R, Masuya M, Inoue N, Shinmei M, Ishii S, Maegawa Y, Maharjan BD, Katayama N, Nosaka T.
    • Journal Title

      PLosONE

      Volume: 16 Issue: 3 Pages: e0248425-e0248425

    • DOI

      10.1371/journal.pone.0248425

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy.2020

    • Author(s)
      Sawaki A, Miyazaki K, Yamaguchi M, Takeuchi T, Kobayashi K, Imai H, Tawara I, Ono R, Nosaka T, Katayama N.
    • Journal Title

      Int J Hematol

      Volume: 111 Issue: 5 Pages: 686-691

    • DOI

      10.1007/s12185-020-02832-x

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Eya2 is critical for E2A-HLF-mediated immortalization of mouse hematopoietic stem/progenitor cells.2019

    • Author(s)
      Maharjan BD, Ono R, Nosaka T.
    • Journal Title

      Int J Oncol

      Volume: 54 Pages: 981-990

    • DOI

      10.3892/ijo.2019.4673

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Tet1 is not necessarily essential for MLL-ENL-induced myeloid leukemia.2021

    • Author(s)
      Ono R, Masuya M, Shinmei M, Ishii S, Maegawa Y, Maharjan BD, Katayama N, Nosaka T.
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 三重大学大学院医学系研究科 感染症制御医学・分子遺伝学

    • URL

      https://www.medic.mie-u.ac.jp/microbiol/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] http://www.medic.mie-u.ac.jp/microbiol/index.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 三重大学大学院医学系研究科 感染症制御医学・分子遺伝学

    • URL

      http://www.medic.mie-u.ac.jp/microbiol/index.html

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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