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Acute Myeloid Leukemia (AML) is the most frequent cause of acute leukemia affecting adults, its incidence increases steadily with age and has been correlated with DNA methylation aberration and inactivation of tumor suppressor genes. Recent epigenomic studies showed that DNA methylation abnormalities have been observed in age related acute myeloid leukemia and indicated the importance of DNA methylation analysis for AML diagnosis. An insight of the connection between DNA methylation and AML might help in development of novel molecular diagnostic and genomic therapies. Epigenetic drugs of two families namely the DNA-demethylating agents and inhibitors of histone deacetylase have emerged as the most promising compounds in this area and several pharmaceutical compounds have received approval for the treatment of specific leukaemia and lymphoma subtypes. In addition possible combination between molecular therapeutic approaches including the activation of certain signal transduction pathway(s) like the interleukins family and chromatin-remodeling events is feasible by the application of epigenetic drugs. This approach might be one of the potential promising solutions for the AML treatment. The present study reviewed recent advances in the research related to genomic and epigenomic of acute myeloid leukemia.