The rationale and use of hypomethylation agents in adult acute myeloid leukemia.

Background: Epigenetic deregulation of gene expression is a newly recognized mechanism that leads to hematologic malignancies such as leukemia and myelodysplastic syndromes. DNA methylation is one of the most commonly occurring epigenetic events.

Objective/methods: The rationale and use of hypomethylation agents in adult acute myeloid leukemia are discussed. Data in this review came from the published literature.

Results/conclusion: In leukemias, alterations in DNA methylation are characterized by the hypermethylation of several genes. Hypermethylation represses transcription of the promoter regions of tumor suppressor genes leading to gene silencing. This change is reversible making it an important therapeutic target. Drugs such as methyltranferase inhibitors including 5-azacytidine and 5-aza-2'-deoxycytidine, and histone deacetylase inhibitors are being used in the treatment of these hematological malignancies.