Optimization of 6MP dose based on NUDT15 pharmacogenomics

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07836
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: National 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
• Keywords: 癌

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.

Free Research Field

小児造血器疾患

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。