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Epigenetics in Hematologic Malignancies

Guest Editor: Dr. E Estey

“Epigenetics” refers to changes in the gene expression occurring without alterations in DNA sequence. Accumulating evidence indicates that epigenetic abnormalities may underlie the pathogenesis of many types of leukemia. Accordingly targeting these abnormalities is a very plausible approach to leukemia therapy. These possibilities have prompted Leukemia to publish an “Epigenetics in Hematologic Malignancies” Spotlight series. The papers in the series range from the more “basic” to the more “clinical”.

So far Abdel-Wahab and Dey discuss how ASXL1 and BAP1 coordinate to regulate several epigenetic pathways. AXSL1 mutations occur in a wide range of myeloid malignancies and are often associated with poor prognosis while BAP1 is likely a tumor suppressor whose deletion results in a CMML phenotype. In a subsequent paper in the series Schoofs , Berdel, and Mueller-Tidow describe possible origins of the distinctive albeit aberrant methylation profiles that characterize various molecular subtypes of AML. Later in the series, Koh et al. elucidate their work on the physical and functional interactions between RUNX1 and MLL, among the most frequently altered genes in acute leukemia, and the consequences of these interactions for epigenetic regulation of hematopoietic genes. Focusing on specific myeloid diseases Itzykson and Fenaux provide an overview of the origin and role of epigenetic aberrations in MDS pathogenesis and the mechanism of action of “hypomethylating agents” (HMA), the most active drugs in advanced MDS, while Solary et al. describe epigenetic changes and their implications in myeloproliferative neoplasms (MPN), and Estey discusses clinical trials of HMA in AML.