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 Hess

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

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
Volume4
Issue number3
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

Fingerprint

Dimerization
Exons
Up-Regulation
CpG Islands
Proteins
Homeobox Genes
Bone Marrow
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Martin, M. E., Milne, T. A., Bloyer, S., Galoian, K., Shen, W., Gibbs, D., ... Hess, J. (2003). Dimerization of MLL fusion proteins immortalizes hematopoietic cells. Cancer Cell, 4(3), 197-207. https://doi.org/10.1016/S1535-6108(03)00214-9

Dimerization of MLL fusion proteins immortalizes hematopoietic cells. / Martin, Mary Ellen; Milne, Thomas A.; Bloyer, Sebastien; Galoian, Karine; Shen, Weiping; Gibbs, Denise; Brock, Hugh W.; Slany, Robert; Hess, Jay.

In: Cancer Cell, Vol. 4, No. 3, 01.09.2003, p. 197-207.

Research output: Contribution to journalArticle

Martin, ME, Milne, TA, Bloyer, S, Galoian, K, Shen, W, Gibbs, D, Brock, HW, Slany, R & Hess, J 2003, 'Dimerization of MLL fusion proteins immortalizes hematopoietic cells', Cancer Cell, vol. 4, no. 3, pp. 197-207. https://doi.org/10.1016/S1535-6108(03)00214-9
Martin ME, Milne TA, Bloyer S, Galoian K, Shen W, Gibbs D et al. Dimerization of MLL fusion proteins immortalizes hematopoietic cells. Cancer Cell. 2003 Sep 1;4(3):197-207. https://doi.org/10.1016/S1535-6108(03)00214-9
Martin, Mary Ellen ; Milne, Thomas A. ; Bloyer, Sebastien ; Galoian, Karine ; Shen, Weiping ; Gibbs, Denise ; Brock, Hugh W. ; Slany, Robert ; Hess, Jay. / Dimerization of MLL fusion proteins immortalizes hematopoietic cells. In: Cancer Cell. 2003 ; Vol. 4, No. 3. pp. 197-207.
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