Epigenetics of B-ALL

Precursor B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common neoplasms. It is characterized by genetic and epigenetic aberrations. The most remarkable mechanisms involved in epigenetic abnormalities are DNA methylation and acetylation. Methylation of CpG islands in promoter regions and acetylation of lysine residues regulate gene expression. Several studies have shown that patients with B-ALL show aberrant DNA methylation in a genome-wide scale. Histone deacetylases (HDAC) regulate gene expression by removing acetyl groups from lysine residues and histone acetyltransferase (HAT) adds acetyl groups. A hematologic malignancy like B-ALL may be very sensitive to small-molecule inhibitors that target these epigenetic mechanisms and therefore may induce expression of pro-apoptotic factors. Thus, HDAC inhibitors (HDACi), DNA methyltransferase inhibitors (DNMTi) and histone acetyltransferase inhibitors (HATi) have been developed as therapies. The objective of this review is to summarize the different epigenetic mechanisms involved in B-ALL.