Aberrant DNA methylation of PTPRG as one possible mechanism of its under-expression in CML patients in the State of Qatar

Mol Genet Genomic Med. 2020 Oct;8(10):e1319. doi: 10.1002/mgg3.1319. Epub 2020 Jul 23.

Abstract

Background: Several studies showed that aberrant DNA methylation is involved in leukemia and cancer pathogenesis. Protein tyrosine phosphatase receptor gamma (PTPRG) expression is a natural inhibitory mechanism that is downregulated in chronic myeloid leukemia (CML) disease. The mechanism behind its downregulation has not been fully elucidated yet.

Aim: This study aimed to investigate the CpG methylation status at the PTPRG locus in CML patients.

Methods: Peripheral blood samples from CML patients at time of diagnosis [no tyrosine kinase inhibitors (TKIs)] (n = 13), failure to (TKIs) treatment (n = 13) and healthy controls (n = 6) were collected. DNA was extracted and treated with bisulfite treatment, followed by PCR, sequencing of 25 CpG sites in the promoter region and 26 CpG sites in intron-1 region of PTPRG. The bisulfite sequencing technique was employed as a high-resolution method.

Results: CML groups (new diagnosed and failed treatment) showed significantly higher methylation levels in the promoter and intron-1 regions of PTPRG compared to the healthy group. There were also significant differences in methylation levels of CpG sites in the promoter and intron-1 regions amongst the groups.

Conclusion: Aberrant methylation of PTPRG is potentially one of the possible mechanisms of PTPRG downregulation detected in CML.

Keywords: CML; PTPRG; Qatar; aberrant DNA; cancer; epigenetics; methylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CpG Islands
  • DNA Methylation*
  • Female
  • Humans
  • Introns
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Promoter Regions, Genetic
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / blood
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / genetics*

Substances

  • PTPRG protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5