Pharmacoepigenetics in childhood acute lymphoblastic leukemia: involvement of miRNA polymorphisms in hepatotoxicity

Epigenomics. 2018 Apr 1;10(4):409-417. doi: 10.2217/epi-2017-0138. Epub 2018 Mar 23.

Abstract

Aim: Hepatotoxicity is one of the most common drug-related toxicities during the treatment of childhood acute lymphoblastic leukemia (ALL). Many genes involved in liver-specific signaling pathways are tightly controlled by miRNAs, and miRNA function could be modulated by SNPs. As a consequence, we hypothesized that variants in miRNAs could be associated with drug-induced hepatotoxicity.

Methods: We analyzed 213 SNPs in 206 miRNAs in a cohort of 179 children with ALL homogeneously treated.

Results: rs2648841 in miR-1208 was the most significant SNP during consolidation phase after false discovery rate correction, probably through an effect on its target genes DHFR, MTR and MTHFR.

Conclusion: These results point out the possible involvement of SNPs in miRNAs in toxicity to chemotherapy in children with ALL.

Keywords: SNPs; chemotherapy; childhood acute lymphoblastic leukemia; hepatotoxicity; methotrexate; miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Genetic Association Studies
  • Humans
  • Infant
  • Liver / drug effects*
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Nucleic Acid Conformation
  • Polymorphism, Single Nucleotide*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Retrospective Studies

Substances

  • Antimetabolites, Antineoplastic
  • MicroRNAs
  • Methotrexate