Epigenetics of Acute Lymphocytic Leukemia

The term epigenetics refers to the study of a number of biochemical modifications of chromatin that have an impact on gene expression regulation. Aberrant epigenetic lesions, in particular DNA methylation of promoter associated CpG islands, are common in acute lymphocytic leukemia (ALL). Recent data from multiple laboratories indicate that several hundred genes, involving dozens of critical molecular pathways, are epigenetically suppressed in ALL. Because these lesions are potentially reversible, the reactivation of these pathways using, for instance, hypomethylating agents may have therapeutic potential in this disease. Furthermore, the analysis of epigenetic alterations in ALL may allow: (1) identification of subsets of patients with poor prognosis when treated with conventional therapy; (2) development of new techniques to evaluate minimal residual disease; (3) better understanding of the differences between pediatric and adult ALL; and (4) new therapeutic interventions by incorporating agents with hypomethylating activity to conventional chemotherapeutic programs. In this review, we describe the role of epigenetic alterations in ALL from a translational perspective.