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Epigenetic deregulation in myeloid malignancies

Published:April 24, 2014DOI:https://doi.org/10.1016/j.trsl.2014.04.012
      Abnormal epigenetic patterning commonly is observed in cancer, including the myeloid malignancies acute myeloid leukemia and myelodysplastic syndromes. However, despite the universal nature of epigenetic deregulation, specific subtypes of myeloid disorders are associated with distinct epigenetic profiles, which accurately reflect the biologic heterogeneity of these disorders. In addition, mutations and genetic alterations of epigenetic-modifying enzymes frequently have been reported in these myeloid malignancies, emphasizing the importance of epigenetic deregulation in the initiation, progression, and outcome of these disorders. These aberrant epigenetic modifiers have become new targets for drug design, because their inhibition can potentially reverse the altered epigenetic landscapes that contribute to the development of the leukemia. In this review, we provide an overview of the role of epigenetic deregulation in leukemic transformation and their potential for therapeutic targeting.

      Abbreviations:

      α-KG (alpha-ketoglutarate), 2-HG (2-hydroxyglutarate), 5hmC (5-hydroxymethylcytosine), 5mC (5-methylcytosine), AML (acute myeloid leukemia), ASXL1 (additional sex combs-like 1), AZA (azacytidine), CMML (chronic myelomonocytic leukemia), DAC (decitabine), DNMT3A (DNA methyltransferase 3A), DNMTi (DNA methyltransferase inhibitor), DOT1L (disruptor of telomeric silencing 1-like), EZH2 (enhancer of zestes 2), FH (fumarate hydratase), HDAC (histone deacetylase), HDACi (histone deacetylase inhibitor), HOXA9 (homeobox A9), HSC (hematopoietic stem cell), JARID2 (Jumonji, AT-rich domain 2), JmjC (Jumonji C), IDH1 (isocitrate dehydrogenase 1), IDH2 (isocitrate dehydrogenase 2), MBM (menin binding motif), MDS (myelodysplastic syndrome), MLL (mixed lineage leukemia), MPN (myeloproliferative neoplasm), MEIS1 (myeloid ecotropic viral integration site 1), NPM1 (nucleophosmin), PRC2 (polycomb repressive complex 2), SDH (succinate dehydrogenase), TET (ten-eleven translocation)
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