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Strategy aiming at the inhibition of leukemic evolution of the myelodysplastic syndromes by the use of MDS-derived cell lines

Research Project

Project/Area Number 20H03582
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionKawasaki Medical School

Principal Investigator

Tohyama Kaoru  川崎医科大学, 医学部, 教授 (80227561)

Co-Investigator(Kenkyū-buntansha) 通山 由美  姫路獨協大学, 薬学部, 教授 (70362770)
片岡 浩巳  川崎医療福祉大学, 医療技術学部, 教授 (80398049)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Keywords骨髄異形成症候群 / 白血病化 / 遺伝子変異 / シングルセル解析
Outline of Research at the Start

骨髄異形成症候群(MDS)は、血球減少に加えて急性骨髄性白血病(AML)に移行しやすい難治性造血障害であるが、発症と病型進展のメカニズム、さらには有効な治療法が見出せていない。応募者は独自に樹立したMDS由来細胞株を用いて、どのようなゲノム背景をもつクローンが次の、より悪性化した細胞集団を形成し、クローンとして病型進展していくのかについて分子機構を探索し、病型移行を阻止する新しい治療戦略への基盤を築くことを目指す。

Outline of Final Research Achievements

To explore the molecular mechanism of disease progression from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), we performed single-cell RNA sequencing analysis using a series of six cell lines established from a patient with MDS. We attempted to explore the molecular mechanisms by which clones with different gene expression profiles develop the malignant process.
In the process of transformation from MDS-like to AML-like, we found a clear increase in CD34-positive cell fraction, loss of functional molecules specific to granulocytes such as S100A8, as well as changes in specific gene clusters. We expect to be able to identify a small number of candidate genes that may play key roles in this process, and further analysis is underway.

Academic Significance and Societal Importance of the Research Achievements

MDSは血球減少に加えてAMLに移行しやすい難治性造血障害で、とくにMDS由来のAMLはきわめて予後不良のため、画期的治療法が待望されている。本研究では申請者が樹立したMDSからAMLへの移行を表現した細胞株を用いて、悪性転換の鍵となる遺伝子変化を突き止めることに繋がることが期待される。解析すべきデータが膨大なため、さらに検討を進める必要があるが、新規治療の開拓に向けてあらたな分子標的を発見できる可能性がある。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (4 results)

All 2022 2021 Other

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

  • [Journal Article] Histone deacetylase inhibitor, panobinostat, exerts anti-proliferative effect with partial normalization from aberrant epigenetic states on granulosa cell tumor cell lines.2022

    • Author(s)
      Hazama Y, Tsujioka T, Kitanaka A, Tohyama K, Shimoya K.
    • Journal Title

      PLoS One.

      Volume: 17(7) Issue: 7 Pages: 0271245-0271245

    • DOI

      10.1371/journal.pone.0271245

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preclinical characterisation and development of a novel myelodysplastic syndrome‐derived cell line2021

    • Author(s)
      Shafiee Sahba、Gelebart Pascal、Popa Mihaela、Helles?y Monica、Hovland Randi、Brendsdal Forthun Rakel、Lee Jungwoo、Tohyama Kaoru、Molven Anders、Parekkadan Biju、Tore Gjertsen Bj?rn、Olsnes Kittang Astrid、McCormack Emmet
    • Journal Title

      British Journal of Haematology

      Volume: 193 Issue: 2 Pages: 415-419

    • DOI

      10.1111/bjh.17372

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] VLX1570 induces apoptosis through the generation of ROS and induction of ER stress on leukemia cell lines2021

    • Author(s)
      Kurozumi N, Tsujioka T, Ouchida M, Sakakibara K, Nakahara T, Suemori SI, Takeuchi M, Kitanaka A, Shibakura M, Tohyama K
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 8 Pages: 3302-3313

    • DOI

      10.1111/cas.14982

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Remarks] 川崎医科大学検査診断学(病態解析学)ホームページ

    • URL

      https://m.kawasaki-m.ac.jp/labhematology/

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report 2020 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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