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Optimization of 6MP dose based on NUDT15 pharmacogenomics

Research Project

Project/Area Number 18K07836
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Osumi Tomoo  国立研究開発法人国立成育医療研究センター, 小児がんセンター, 医長 (00383878)

Co-Investigator(Kenkyū-buntansha) 加藤 元博  国立研究開発法人国立成育医療研究センター, 小児血液・腫瘍研究部, 診療部長 (40708690)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords癌 / 急性リンパ性白血病 / オーダーメード医療 / 薬剤感受性 / 遺伝子多型 / 急性リンパ芽球性白血病 / リンパ芽球性リンパ腫 / メルカプトプリン (6MP) / NUDT15遺伝子 / ファーマコゲノミクス
Outline of Final Research Achievements

6-mercaputourine (6MP) is an essential drug in treatment for acute lymphoblastic leukemia/lymphoma in children, and interindividual difference sensitivity has been widely recognized. In this study, we focused on NUDT15 polymorphisms which confer sensitivity to 6-MP. First, investigation of association between outcome and NUDT15 revealed that NUDT15 did not affect outcome of leukemia, which suggested appropriate reduction for those with NUDT15 variants could maintain therapeutic effect. Second, questionnaire survey for bi-allelic NUDT15 variants showed that average dose of 6MP was only 5.2 mg/m2 for bi-allelic NUDT15 cases.

Academic Significance and Societal Importance of the Research Achievements

NUDT15を主なテーマとして、事前の多型タイピングに基づく適切な用量設定により、合併症の回避をしつつ李朝効果を維持できることを示した。ファーマコゲノミクスの成功例として、診療に実装するためのエビデンスにつながる。

Report

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

    (10 results)

All 2021 2019 2018 Other

All Int'l Joint Research (5 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] シンガポール国立大学(シンガポール)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] St. Jude Children's Research Hospital(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] St. Jude Children's Research Hospital(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2018 Research-status Report
  • [Journal Article] An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia2021

    • Author(s)
      Tanaka Y et al.
    • Journal Title

      Haematologica

      Volume: Epub ahead of print Issue: 7 Pages: 2026-2029

    • DOI

      10.3324/haematol.2020.266320

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diplotype analysis of NUDT15 variants and 6-mercaptopurine sensitivity in pediatric lymphoid neoplasms2018

    • Author(s)
      Tsujimoto S, Osumi T, Uchiyama M, Shirai R, Moriyama T, Nishii R, Yamada Y, Kudo K, Sekiguchi M, Arakawa Y, Yoshida M, Uchiyama T, Terui K, Ito S, Koh K, Takita J, Ito E, Tomizawa D, Manabe A, Kiyokawa N, Yang JJ, Kato M.
    • Journal Title

      Leukemia

      Volume: 32 Issue: 12 Pages: 2710-2714

    • DOI

      10.1038/s41375-018-0190-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Recent updates of NUDT152019

    • Author(s)
      Kato M
    • Organizer
      1st Annual Meeting of the European Society for Pediatric Oncology2
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] NUDT15 Variants Confer High Incidence of Secondary Malignancies of ALL in Children2019

    • Author(s)
      Yoshida M
    • Organizer
      61th Annual Meeting of the American Society of Hematology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] NUDT15 and 6-MP individualization2018

    • Author(s)
      Kato M, Osumi T, Moriyama T, Sanada M, Yang JJ, Manabe A, Koh K
    • Organizer
      第29回国際BFM会議
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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

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