RT Book, Section A1 Cairns, Bradley R. A2 Kaushansky, Kenneth A2 Lichtman, Marshall A. A2 Prchal, Josef T. A2 Levi, Marcel M. A2 Press, Oliver W. A2 Burns, Linda J. A2 Caligiuri, Michael SR Print(0) ID 1121089335 T1 Epigenetics T2 Williams Hematology, 9e YR 2015 FD 2015 PB McGraw-Hill Education PP New York, NY SN 9780071833004 LK hemonc.mhmedical.com/content.aspx?aid=1121089335 RD 2024/03/28 AB SUMMARYEpigenetics involves a heritable change in phenotype without a change in genotype–with the inheritance of particular chromatin and transcription states often underlying the mechanism. Chromatin regulates gene expression by controlling the density and positioning of nucleosomes, and by the use of histone- and DNA-modifying enzymes. Chromatin and transcription factors drive proper differentiation decisions through their coregulation of key factors in development and proliferation. Of particular interest to hematologists are instances when misregulation/mutation of chromatin factors drives hematologic malignancies and myeloproliferative disorders. Here, fusion proteins that involve the mistargeting of chromatin regulators have been known for decades. More recently, high-throughput sequencing and other genomics approaches have revealed mutations in many types of chromatin regulators in hematologic malignancies, including mutations in chromatin remodelers, DNA methylation regulators, histone modification enzymes, and metabolic enzymes affecting epigenetic cofactors. Overall, these studies reveal a consistent theme: epigenetic and genetic mutations confer both variation and plasticity to the transcriptome, and when combined with selection, arrive at transcriptomes that promote proliferation, survival, and adaptability. This chapter addresses these mechanistic principles of chromatin, and their misregulation in hematologic malignancies, as well as emerging therapeutic approaches.