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

  • Progress in Hematology
  • Chromatin regulation in leukemogenesis
  • Published:
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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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Acknowledgments

Jay Hess is supported in part through funding from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pathology, Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, 5215 Medical Science 1, SPC 5602, Ann Arbor, MI, 48109-5602, USA

    Yali Dou

  2. Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, 5240 Medical Science 1, SPC 5602, Ann Arbor, MI, 48109-5602, USA

    Jay L. Hess

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Dou, Y., Hess, J.L. Mechanisms of transcriptional regulation by MLL and its disruption in acute leukemia. Int J Hematol 87, 10–18 (2008). https://doi.org/10.1007/s12185-007-0009-8

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