Emerging role of NUDT15 polymorphisms in 6-mercaptopurine metabolism and dose related toxicity in acute lymphoblastic leukaemia

Leuk Res. 2017 Nov:62:17-22. doi: 10.1016/j.leukres.2017.09.012. Epub 2017 Sep 25.

Abstract

Despite more than 80% long term survival in ALL, morbidity due to drug related myelotoxicity remains high. Germline variants of thiopurine metabolizing enzymes (TPMT and ITPA) have been described which are associated with increased drug toxicity during maintenance phase, but their prevalence in different ethnic groups is variable to account for relatively high myelotoxicity incidence. NUDT15 variant (rs116855232) has been recently identified as a novel polymorphism related with thiopurine-induced leucopenia in inflammatory bowel disease and ALL. Current review highlights the scientific data on NUDT15 enzyme variant and its relation to 6-MP toxicity in various ethnic populations.

Keywords: 6-Mercaptopurine; Myelotoxicity; NUDT15; Single nucleotide polymorphism.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / metabolism
  • Humans
  • Mercaptopurine / adverse effects*
  • Mercaptopurine / metabolism
  • Polymorphism, Single Nucleotide
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Pyrophosphatases / genetics*

Substances

  • Antimetabolites, Antineoplastic
  • Mercaptopurine
  • NUDT15 protein, human
  • Pyrophosphatases