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