Pharmacogenetic evaluation of 6-mercaptopurine-mediated toxicity in pediatric acute lymphoblastic leukemia patients from a South Indian population

Pharmacogenomics. 2021 May;22(7):401-411. doi: 10.2217/pgs-2020-0193. Epub 2021 Apr 20.

Abstract

Aim: To evaluate the variants in the genes coding for the proteins involved in thiopurine and folate metabolism with treatment related adverse effects (TRAEs). Materials & methods: Eleven variants in seven candidate genes were genotyped in 127 pediatric acute lymphoblastic leukemia patients under 6-mercaptopurine (6-MP) treatment to infer the association of selected genotypes with TRAEs. Results: Among the genotypes inspected, NUDT15 (c.415C>T) and SLC19A1 (c.80G>A) showed a significant association with the TRAEs (odds ratio = 4.01, p = 0.002 and odds ratio = 7.78, p = 0.002). Conclusion:SLC19A1 and NUDT15 play an important role in the metabolism of 6-MP and it is necessary to spot other variants in associated pathways and investigate the factors that can impact 6-MP metabolism.

Keywords: 6-mercaptopurine; NUDT15; SLC19A1; TPMT; acute lymphoblastic leukemia; genetic markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antimetabolites, Antineoplastic / toxicity*
  • Child
  • Child, Preschool
  • Cyclophosphamide / analogs & derivatives
  • Female
  • Genetic Markers / genetics
  • Humans
  • India
  • Male
  • Mercaptopurine / therapeutic use
  • Mercaptopurine / toxicity*
  • Polymorphism, Single Nucleotide / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Pyrophosphatases / genetics
  • Reduced Folate Carrier Protein / genetics

Substances

  • Antimetabolites, Antineoplastic
  • Genetic Markers
  • Reduced Folate Carrier Protein
  • SLC19A1 protein, human
  • Cyclophosphamide
  • Mercaptopurine
  • NUDT15 protein, human
  • Pyrophosphatases
  • trofosfamide