Epigenetic modifiers in normal and malignant hematopoiesis.
Genome scale sequencing in patients with cancer has revealed a lower frequency of genetic aberrations in hematologic disorders compared with most other malignancies, suggesting a prominent role for epigenetic mechanisms. In parallel, epigenetic modifiers that are altered in cancer play critical roles in normal hematopoietic development, influencing both self-renewal of hematopoietic stem cells and differentiation into the different lineages. In this review, we aim to compare the role of several key DNA or histone modifying enzymes and complexes in normal development and hematopoietic malignancies, including DNMT3A, TET2, IDH1, IDH2, MLL1, MLL4, DOT1L, PRC1/2 and WSHC1/NSD2/MMSET. Insights into their biological mechanisms led to the development of therapies designed to target mutant IDH1 and IDH2, DOT1L in MLL-rearranged leukemias and EZH2 in several cancer types including lymphomas. Inhibitors for these enzymes are currently in clinical trials.
['Haladyna|Jessica N|JN|', 'Yamauchi|Taylor|T|', 'Neff|Tobias|T|', 'Bernt|Kathrin M|KM|']
D000818:Animals D004248:DNA (Cytosine-5-)-Methyltransferases D000090205:DNA Methyltransferase 3A D004268:DNA-Binding Proteins D049308:Dioxygenases D044127:Epigenesis, Genetic D019337:Hematologic Neoplasms D006410:Hematopoiesis D011495:Histone-Lysine N-Methyltransferase D006801:Humans D007521:Isocitrate Dehydrogenase D008780:Methyltransferases D051379:Mice D051788:Myeloid-Lymphoid Leukemia Protein D063146:Polycomb-Group Proteins D011518:Proto-Oncogene Proteins D012097:Repressor Proteins
epigenetics DNMT3A TET2 DOT1L PRC1/2 WSHC1/NSD2/MMSET leukemia EZH2 IDH MLL