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Genetic dissection of molecular mechanisms in ATL

Research Project

Project/Area Number 16H06249
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionNational Cancer Center Japan (2017-2018)
Kyoto University (2016)

Principal Investigator

Keisuke Kataoka  国立研究開発法人国立がん研究センター, 研究所, 分野長 (90631383)

Research Collaborator Shimoda Kazuya  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2016: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Keywords癌 / 成人T細胞白血病リンパ腫 / 遺伝学 / 成人細胞白血病リンパ腫 / 遺伝子解析 / 遺伝子異常 / 遺伝子改変モデル
Outline of Final Research Achievements

We investigated the association between genetic alterations and disease status in ATL. We found that TP53 and IRF4 mutations as well as numerous copy number alterations were associated with aggressive ATL (acute and lymphoma subtypes). By contrast, STAT3 mutations were related to chronic and smoldering subtypes. In addition, we analyzed the effect of genetic alterations on patient survival. We found that a set of genetic alterations, particularly PD-L1 copy number amplifications, were associated with worse prognosis even when established clinical prognostic factors were adjusted.
We also developed a novel transgenic mouse model harboring the PRKCB D427 mutation. We analyzed this model, but found no phenotype in the immune and hematopoietic systems.

Academic Significance and Societal Importance of the Research Achievements

本研究により、臨床的因子と独立して予後不良と関連する遺伝子異常を同定することが出来た。この結果、臨床的な重要性に基づいた上で治療標的として有用な遺伝子異常が同定されたことのみならず、ATLにおける遺伝子異常のバイオマーカー(予後因子)として有用性が解明され、治療方針の決定に役立つ予後予測モデルの確立に繋がることが期待される。

Report

(3 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (3 results)

All 2017

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

  • [Journal Article] Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma2017

    • Author(s)
      Kataoka Keisuke、Iwanaga Masako、Yasunaga Jun-ichirou、et al.
    • Journal Title

      Blood

      Volume: 131 Issue: 2 Pages: 215-225

    • DOI

      10.1182/blood-2017-01-761874

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 成人T細胞白血病リンパ腫におけるゲノム異常とその臨床的意義2017

    • Author(s)
      片岡圭亮
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Prognostic Relevance of Integrated Genetic Profiling in Adult T-cell Leukemia/Lymphoma2017

    • Author(s)
      Yotaro Ochi, Keisuke Kataoka, Masako Iwanaga, et al.
    • Organizer
      18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      横浜
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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