GPX3 promoter is methylated in chronic myeloid leukemia

Int J Clin Exp Pathol. 2015 Jun 1;8(6):6450-7. eCollection 2015.

Abstract

Hypermethylation of GPX3 (glutathione peroxidase 3) promoter has been identified in various cancers. However, the pattern of GPX3 promoter methylation in chronic myeloid leukemia (CML) remains unknown. Our study was aimed to investigate the methylation status of GPX3 promoter and its clinical relevance in CML. Real-time quantitative methylation-specific PCR and bisulfite sequencing PCR was performed to detect the level of GPX3 methylation in 80 CML patients and 44 controls. GPX3 promoter in CML patients was significantly methylated compared with controls (P = 0.007). GPX3 highly methylated patients showed significantly older age than GPX3 lowly methylated patients (P = 0.037). However, patients with GPX3 methylation had significantly lower white blood cells than those with low GPX3 methylation (P = 0.006). BCR-ABL transcript in GPX3 highly methylated patients was a little lower than that in GPX3 lowly methylated patients (P = 0.161). No significant differences were observed in the frequency of GPX3 methylation in the different stages of CML (P = 1.000). Significantly negative correlation was observed between GPX3 expression and GPX3 methylation (R = -0.442, P = 0.004). GPX3 mRNA level in K562 cell line was significantly increased after 5-aza-2'-deoxycytidine treatment, and GPX3 methylation level was decreased. GPX3 hypermethylation is frequent in CML and is negatively associated with its expression.

Keywords: GPX3; chronic myeloid leukemia; expression; methylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Case-Control Studies
  • DNA Methylation* / drug effects
  • DNA Modification Methylases / antagonists & inhibitors
  • DNA Modification Methylases / metabolism
  • Decitabine
  • Enzyme Inhibitors / pharmacology
  • Epigenesis, Genetic* / drug effects
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glutathione Peroxidase / genetics*
  • Glutathione Peroxidase / metabolism
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics
  • Young Adult

Substances

  • BCR-ABL1 fusion protein, human
  • Enzyme Inhibitors
  • RNA, Messenger
  • Decitabine
  • GPX3 protein, human
  • Glutathione Peroxidase
  • DNA Modification Methylases
  • Fusion Proteins, bcr-abl
  • Azacitidine