The Myelodysplastic Syndromes (MDS) are a group of clonal disorders of the hematopoietic system characterized by the presence of ineffective hematopoiesis, peripheral cytopenias and an increased risk of transformation to acute myeloid leukemia (AML). The pathogenesis of MDS involves a complex pattern of genetic, epigenetic and immune mediated mechanisms. However, recent advances in the understanding of the disease have identified altered epigenetic mechanisms, particularly aberrant DNA methylation as a key pathogenic factor in MDS. Since presently very sparse data is available on the epigenetic regulators and their effect on the methylation machinery, we studied the mutations in the epigenetic regulators i.e. JAK2V617F and IDH-2 ina series of 45 MDS patients and analyzed their effect on the methylation of the four tumor suppressor genes (p15, FHIT, calcitonin and SOCS-1) and clinical profile of MDS patients. We have found JAK2 mutation in 29% and IDH2 in 7% of MDS cases. JAK2 mutation was significantly correlated with the SOCS-1 gene methylation (p<0.05). No effect of IDH2 mutation on methylation was observed. Also, we did not find any correlation of co-occurrence of JAK2 /IDH2 mutation and SOCS -1 methylation on the prognosis and treatment outcome. Our study suggests the importance of epigenetic regulation of SOCS -1 methylation through JAK/STAT pathway in the leukemogenesis.