Involvement of miRNA polymorphism in mucositis development in childhood acute lymphoblastic leukemia treatment

Pharmacogenomics. 2018 Dec;19(18):1403-1412. doi: 10.2217/pgs-2018-0113.

Abstract

Aim: Mucositis, linked to methotrexate, daunorubicin or cyclophosphamide, is a frequent childhood acute lymphoblastic leukemia (ALL) therapy side effect. miRNAs regulate the expression of pharmacokinetic/pharmacodynamic pathway genes. SNPs in miRNAs could affect their levels or function, and affect their pharmacokinetic/pharmacodynamic pathway target genes. Our aim was to determine the association between miRNA genetic variants targeting mucositis-related genes and mucositis-developing risk.

Patients & methods: We analyzed 160 SNPs in 179 Spanish children with B-cell precursor ALL homogeneously treated with LAL/SHOP protocols.

Results: We identified three SNPs in miR-4268, miR-4751 and miR-3117 associated with mucositis, diarrhea and vomiting, respectively.

Conclusion: The effect of these SNPs on genes related to drug pharmacokinetics/pharmacodynamics could explain mucositis, diarrhea and vomiting development during ALL therapy.

Keywords: SNP; acute lymphoblastic leukemia; chemotherapy; miRNA; mucositis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Mucositis / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Retrospective Studies

Substances

  • MicroRNAs