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01-01-2008 | Progress in Hematology

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

Authors: Yali Dou, Jay L. Hess

Published in: International Journal of Hematology | Issue 1/2008

Abstract

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

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Title: Mechanisms of transcriptional regulation by MLL and its disruption in acute leukemia
Authors: Yali Dou
Jay L. Hess
Publication date: 01-01-2008
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 1/2008
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-007-0009-8

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