DNA methylation changes following 5-azacitidine treatment in patients with myelodysplastic syndrome

J Korean Med Sci. 2011 Feb;26(2):207-13. doi: 10.3346/jkms.2011.26.2.207. Epub 2011 Jan 24.

Abstract

DNA methyltransferase inhibitor, 5-azacitidine (AC) is effective in myelodysplastic syndromes (MDS) and can induce re-expression in cancer. We analyzed the methylation of 25 tumor suppressor genes in AC-treated MDS. Hypermethylation of CDKN2B, FHIT, ESR1, and IGSF4 gene was detected in 9/44 patients. In concordance with the clinical response, a lack of or decreased methylation in 4 patients with hematologic improvements and persistent methylation in 4 others with no response was observed. The mRNA expression of CDKN2B, IGSF4, and ESR1 was significantly reduced in MDS. Our results suggest that methylation changes contribute to disease pathogenesis and may serve as marker to monitor the efficacy of treatments.

Keywords: Azacitidine; DNA Methylation; DNA Methyltransferase Inhibitors; Demethylation; MS-MLPA; Myelodysplastic Syndromes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Azacitidine / pharmacology*
  • Azacitidine / therapeutic use*
  • DNA Methylation / drug effects*
  • DNA Modification Methylases / antagonists & inhibitors
  • DNA Modification Methylases / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / genetics*
  • Young Adult

Substances

  • Enzyme Inhibitors
  • DNA Modification Methylases
  • Azacitidine