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CRISPR-Cas9 screen identifies essential chromatin-remodeling factors and novel therapeutic targets for acute myeloid leukemia

Research Project

Project/Area Number 18K16089
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKyoto University (2019-2020)
Kyushu University (2018)

Principal Investigator

Yuichiro Semba  京都大学, 医学研究科, 特別研究員(PD) (90816787)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords急性骨髄性白血病 / CRISPRスクリーニング / 白血病 / クロマチンリモデリング因子 / CRISPR-Cas9 screening
Outline of Final Research Achievements

Acute myeloid leukemia (AML) is a devastating disease with low long-term survival rates, underscoring the critical need to devise a novel therapeutic strategy. In this study, we focused on the epigenetic regulating system, especially on the chromatin remodeling factors, and hypothesized that these factors play essential roles in AML cell survival in concert with transcription factors. Since there is a limitation to the conventional method of targeting individual factors in elucidating the complicated epigenetic regulating system involved, we instead performed genome-wide CRISPR-Cas9 screens to comprehensively identify the chromatin remodeling factors essential to AML cell survival and analyzed their functions.

Academic Significance and Societal Importance of the Research Achievements

本研究者は、AML細胞の維持に重要な転写因子およびクロマチンリモデリング因子を同定するため、CRISPR-Cas9システムによる全ゲノムスクリーニングの実験系を確立した。このスクリーニングの結果から、AML細胞増殖に必須である、または腫瘍抑制因子として機能するエピゲノム制御関連遺伝子を抽出可能であった。さらに、予後不良AMLに遺伝子異常が高頻度に認められる転写因子TP53に注目し、各因子についてTp53 pathway依存性を明らかにした。本研究の結果から、AMLにおいて転写因子が制御するエピゲノム制御因子が明らかとなり、本知見は今後の新たなAML治療開発につながることが期待される。

Report

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

    (5 results)

All 2020 2019

All Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Presentation] 網羅的全ゲノム編集技術を駆使したTP53変異白血病の新規治療標的探索2020

    • Author(s)
      Semba Y, Yamauchi T, Nakao F, Nogami J, Canver MC, Pinello L, Bauer DE, Akashi K and Maeda T.
    • Organizer
      第118回日本内科学会講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CRISPR-Cas9 Screen Identifies XPO7 As a Potential Therapeutic Target for TP53-Mutated AML.2019

    • Author(s)
      Semba Y, Yamauchi T, Nakao F, Nogami J, Canver MC, Pinello L, Bauer DE, Akashi K and Maeda T.
    • Organizer
      The 61st American Society of Hematology (ASH) Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genome-wide CRISPR-Cas9 screen identifies novel therapeutic targets for TP53-mutated AML.2019

    • Author(s)
      Semba Y, Yamauchi T, Nakao F, Yao Q, Nogami J, Canver MC, Pinello L, Bauer DE, Akashi K and Maeda T.
    • Organizer
      The 81st Annual Meeting of the Japanese Society of Hematology (JSH)
    • Related Report
      2019 Research-status Report
  • [Presentation] CRISPR-Cas9 Screen Identifies XPO7 as a Novel Therapeutic Target for TP53-mutated AML.2019

    • Author(s)
      Semba Y, Yamauchi T, Nakao F, Yao Q, Nogami J, Canver MC, Pinello L, Bauer DE, Akashi K and Maeda T.
    • Organizer
      The seventh annual meeting of the Society of Hematologic Oncology (SOHO)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] CRISPR-Cas9 screen identifies XPO7 as a novel therapeutic target for TP53-mutated AML.2019

    • Author(s)
      Semba Y, Yamauchi T, Nakao F, Nogami J, Yao Q, Canver MC, Pinello L, Bauer DE, Akashi K, Maeda T.
    • Organizer
      The FASEB Hematologic Malignancies Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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

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