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Development of a novel therapy targeting alteration of lipid metabolism in leukemia

Research Project

Project/Area Number 20K17369
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Mizuno Hideaki  東京大学, 医学部附属病院, 助教 (70869594)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords急性骨髄性白血病 / 脂質代謝 / 白血病
Outline of Research at the Start

急性骨髄性白血病は依然として難治性の疾患であり新規治療標的の開発が望まれている。近年、細胞内の主要代謝経路の変容が生み出す癌細胞独自の代謝様式が癌細胞の脆弱性につながることがわかってきた。そこで本研究では白血病細胞を用いて白血病の脂質代謝プロファイルを解析し、新規治療標的の同定を行うことを目指す。更に脂質代謝経路が実際に治療標的となり得るかを検証し、本領域における新規治療標的開発の基盤とすることを目的とする。

Outline of Final Research Achievements

It is becoming clear that unique metabolic patterns created by alterations in key intracellular metabolic pathways such as glucose and amino acid metabolism in leukemia are involved in leukemia stemness and chemotherapy resistance. On the other hand, vulnerabilities generated by these metabolic alteration can be novel therapeutic targets. This study aims to establish a novel therapy by targeting lipid metabolism in leukemia. We have shown that several genes involved in cholesterol metabolism are aberrantly expressed in leukemia cells. In this study, we evaluated the effects of inhibiting these genes and metabolic pathways.

Academic Significance and Societal Importance of the Research Achievements

難治性白血病であるEVI1高発現白血病マウスモデル、公開データベースによる急性骨髄性白血病患者のmRNAと予後の解析、治療抵抗性急性骨髄性白血病患者検体の単一細胞トランスクリプトーム解析のそれぞれから、脂質代謝経路の遺伝子発現異常が治療抵抗性に関与していると考えられる結果が得られた。これらの代謝経路の主要細胞における機能的な探索を今後継続して行う必要があるが、難治性白血病の新規治療法開発につながる成果が得られた。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] CCDC88C-FLT3 gene fusion in CD34-positive haematopoietic stem and multilineage cells in myeloid/lymphoid neoplasm with eosinophilia.2022

    • Author(s)
      Kurihara Y, Mizuno H, Honda A, Shimura A, Fujioka Y, Maki H, Kurokawa M.
    • Journal Title

      Journal of cellular and molecular medicine

      Volume: 26 Issue: 3 Pages: 950-952

    • DOI

      10.1111/jcmm.17143

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CAMK2G is identified as a novel therapeutic target for myelofibrosis.2022

    • Author(s)
      Miyauchi M, Sasaki K, Kagoya Y, Taoka K, Masamoto Y, Yamazaki S, Arai S, Mizuno H, Kurokawa M.
    • Journal Title

      Blood Advances

      Volume: 6 Issue: 5 Pages: 1585-1597

    • DOI

      10.1182/bloodadvances.2020003303

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evi1 upregulates Fbp1 and supports progression of acute myeloid leukemia through pentose phosphate pathway activation.2021

    • Author(s)
      Mizuno H, Koya J, Masamoto Y, Kagoya Y, Kurokawa M.
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 10 Pages: 4112-4126

    • DOI

      10.1111/cas.15098

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Intrapatient Complex Transcriptional Responses to Conventional Chemotherapy in Relapsed Acute Myeloid Leukemia Revealed By Single Cell RNA-Seq Analysis2021

    • Author(s)
      Hideaki Mizuno, Akira Honda, Mineo Kurokawa
    • Organizer
      63rd ASH annual meeting
    • Related Report
      2021 Annual Research Report
  • [Presentation] Intratumoral complex responses to conventional chemotherapy in AML revealed by single cell RNA-seq2021

    • Author(s)
      Hideaki Mizuno, Akira Honda, Mineo Kurokawa.
    • Organizer
      第83回 日本血液学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Intratumoral complex responses to conventional chemotherapy in AML revealed by single cell RNA-seq2021

    • Author(s)
      Hideaki Mizuno, Akira Honda, Mineo Kurokawa.
    • Organizer
      第80回 日本癌学会学術総会
    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2023-01-30  

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