Identification of genes with different methylation profiles between RAEB and RCMD in myelodysplastic syndrome.

Abstract

6608 Background: Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by significant prognostic heterogeneity and a preleukemic condition with transformation into acute myeloid leukemia. However, the underlying genetic events remain poorly understood. Since aberrant DNA methylation might play a causative role in disease and prognosis, the study investigated the difference of DNA methylation profiles between refractory anemia with excess blast (RAEB) and refractory cytopenia with multilineage dysplasia (RCMD). Methods: Bone marrow samples from 20 patients with primary MDS (nine RAEB and 11 RCMD) and peripheral blood samples from four controls, were assessed using a commercial whole genome-wide methylation assay. Results: The microarray data revealed statistically significant hypermethylation of 69 genes in RAEB, but not in RCMD. The candidate genes mapped to five different networks, with network 1 being the top-scoring network with functions in gene expression, cancer, and cell cycle. Five network 1 genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with disease progression in malignancy. Methylation-specific polymerase chain reaction was used to detect the methylation level of candidate gene promoters in both RAEB and RCMD. Among these genes, methylated promoters of GSTM5 (55.5% and 20%, respectively), BIK (20% and 0%, respectively), and ANGPTL2 (44.4% and 10%, respectively) occurred more frequently in RAEB than in RCMD. Conclusions: Although the functions of these genes were not revealed, DNA methylation of GSTM5, BIK and ANGPTL2 might induce epigenetic silencing and contribute to the increasing blasts, resulting in progression of MDS. No significant financial relationships to disclose.