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

Yali Dou, Jay L. Hess

Research output: Contribution to journalReview article

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10-18
Number of pages9
JournalInternational Journal of Hematology
Volume87
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Keywords

  • Epigenetics
  • Histone methylation
  • Leukemia
  • MLL
  • Trithorax

ASJC Scopus subject areas

  • Hematology

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