Epigenetics and DNA Methylation Modifications

DNA methylation and post-transcriptional histone modifications interact in an epigenetic network crucial for the regulation of chromatin structure and transcriptional activity. Aberrant gene promoter hypermethylation patterns, leading to transcriptional silencing, have been recognized as a key epigenetic mechanism in the process of malignant transformation. The growing list of genes affected by epigenetic changes reveals not only new insights in the molecular pathogenesis of hematopoietic malignancies, but also provides novel biomarkers that may contribute to the improvement of diagnostic methods and prognostic assessment. Moreover, both regional DNA hypermethylation and histone hypoacetylation have been recognized as promising novel therapeutic targets in hematopoietic malignancies. Currently, two hypomethylating agents are in clinical use for myelodysplastic syndromes, 5-azacitidine and 5-aza-2- deoxycytidine (decitabine), with an impact on disease evolution. Our increasing knowledge regarding the epigenetic network that controls the aberrant silencing of cancer-related genes, and how these events interact with genetic alterations to drive tumor progression, may help us derive novel treatment concepts against human cancer.

Keywords: Epigenetic alterations, CpG islands, Histone modifications, CDKN2B/p15, CDKN2A/p16, Chronic Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, DNA Methyltransferase Inhibitors, Histone Deacetylase Inhibitors.