Mechanisms of transcriptional regulation by MLL and its disruption in acute leukemia

摘要: Fusion of the mixed lineage leukemia protein (MLL) to one over 50 different translocation partners converts it into a potent leukemogenic oncoprotein. The resulting fusion proteins transform primarily through upregulation A-cluster Hox genes, including Hoxa9 and cofactor Meis1. Considerable progress has been made in delineating differences between normal gene regulation by MLL deregulated transcription MLL-induced leukemias. Some dimerize truncated molecule. Other appear recruit nuclear coactivator complexes that have diverse enzymatic activities impinge on transcriptional elongation pathways. These activities, RNA polymerase II phosphorylation as well histone H3 lysine 79 methylation present attractive targets for development future MLL-directed therapy.