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Integrated analysis of the molecular basis of leukemia stem cells using a mouse model inducibly developing leukemia

Research Project

Project/Area Number 21K08411
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) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords造血器腫瘍 / 白血病
Outline of Research at the Start

白血病は、血液の「がん」である。骨髄移植などの強力な治療法に加え、白血病細胞を特異的に狙い撃つ分子標的療法の開発などにより、治療成績の向上が図られてきているが、依然として難治性であることが少なくない。そこで、本研究では、白血病細胞の源である白血病幹細胞の根絶につながる、新たな白血病の治療法の開発に役立てる知見を得ることを最終目標として、これまで我々の構築してきた独自の白血病発症モデルマウスを多角的に活用して、最新の分子細胞生物学的観点から、白血病幹細胞の存立基盤を明らかにしていく予定である。

Outline of Final Research Achievements

In this study, using a conditional MLL-ENL transgenic mouse model originally constructed by our group, we focused on the relationship between the undifferentiated nature of hematopoietic cells, which are the mother cells from which leukemia stem cells arise, and found that the more undifferentiated they are, the more likely they are to produce leukemia stem cells. Using a variety of molecular biological techniques, we also found that BAHCC1 plays an important role in the molecular mechanism of MLL-ENL leukemogenesis. Furthermore, we confirmed that BAHCC1 is equally important in human leukemia cells, and submitted the manuscript to Blood Advances for publication, which was accepted.

Academic Significance and Societal Importance of the Research Achievements

本研究で扱っている白血病は、血液系における「がん」と位置付けられる。近年、骨髄移植などの強力な治療法に加えて、時として非常に効果的な分子標的療法の開発により、治療成績において一定の改善が認められてきた。その一方で、こうした恩恵を受けられていないタイプの白血病もまだ少なからず存在しており、新たな治療法の開発が求められている。本研究では、我々などの先行研究により、難治性と相関する、未分化な造血細胞を発症母地とするタイプの白血病のマウスモデルを用いて、従来ほとんど知られていなかった、白血病発症における重要な役割を果たしている新たな分子機構の一端を解明し、今後、新たな治療標的の探索を目指していく。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2024 2023 2022 2021 Other

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results) Remarks (2 results)

  • [Journal Article] Bahcc1 is critical for the aberrant epigenetic program in a mouse model of MLL-ENL-mediated leukemia.2024

    • Author(s)
      Nakamura A, Masuya M, Shinmei M, Tawara I, Nosaka T, Ono R.
    • Journal Title

      Blood Advances

      Volume: - Issue: 9 Pages: 2193-2206

    • DOI

      10.1182/bloodadvances.2023011320

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis.2022

    • Author(s)
      D'Alessandro-Gabazza CN, Yasuma T, Kobayashi T, Toda M, Abdel-Hamid AM, Fujimoto H, Hataji O, Nakahara H, Takeshita A, Nishihama K, Okano T, Saiki H, Okano Y, Tomaru A, D'Alessandro VF, Shiraishi M, Mizoguchi A, Ono R, Ohtsuka J, Fukumura M, Nosaka T, et al. & Gabazza EC
    • Journal Title

      Nat Commun

      Volume: 13 Issue: 1 Pages: 1558-1558

    • DOI

      10.1038/s41467-022-29064-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Non-propagative human parainfluenza virus type 2 nasal vaccine robustly protects the upper and lower airways against SARS-CoV-2.2021

    • Author(s)
      Ohtsuka J, Imai M, Fukumura M, Maeda M, Eguchi A, Ono R, Maemura T, Ito M, Yamayoshi S, Kataoka Y, Kawaoka Y, Nosaka T
    • Journal Title

      iScience

      Volume: 24 Issue: 12 Pages: 103379-103379

    • DOI

      10.1016/j.isci.2021.103379

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Bahcc1 is critical for the aberrant epigenetic program in MLL-ENL-mediated leukemogenesis.2023

    • Author(s)
      Akihide Nakamura, Masahiro Masuya, Isao Tawara, Tetsuya Nosaka, Ryoichi Ono
    • Organizer
      第85回日本血液学会学術集会
    • Related Report
      2023 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
      2023 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
      2022 Research-status Report 2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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