Dimerization of MLL fusion proteins immortalizes hematopoietic cells

Mary Ellen Martin, Thomas A. Milne, Sebastien Bloyer, Karine Galoian, Weiping Shen, Denise Gibbs, Hugh W. Brock, Robert Slany, Jay L. Hess

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


MLL fusion proteins are leukemogenic, but their mechanism is unclear. Induced dimerization of a truncated MLL immortalizes bone marrow and imposes a reversible block on myeloid differentiation associated with upregulation of Hox a7, a9, and Meis1. Both dimerized MLL and exon-duplicated MLL are potent transcriptional activators, suggesting a link between dimerization and partial tandem duplication of DNA binding domains of MLL. Dimerized MLL binds with higher affinity than undimerized MLL to a CpG island within the Hox a9 locus. However, MLL-AF9 is not dimerized in vivo. The data support a model in which either MLL dimerization/exon duplication or fusion to a transcriptional activator results in Hox gene upregulation and ultimately transformation.

Original languageEnglish (US)
Pages (from-to)197-207
Number of pages11
JournalCancer Cell
Issue number3
StatePublished - Sep 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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