Interaction of MLL amino terminal sequences with menin is required for transformation

Corrado Caslini, Zhaohai Yang, Mohamad El-Osta, Thomas A. Milne, Robert K. Slany, Jay Hess

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Rearrangements of the mixed lineage leukemia gene MLL are associated with aggressive lymphoid and myeloid leukemias. The resulting MLL fusion proteins enforce high-level expression of HOX genes and the HOX cofactor MEIS1, which is pivotal for leukemogenesis. Both wild-type MLL and MLL fusion proteins interact with the tumor suppressor menin and with the Hoxa9 locus in vivo. Here, we show that MLL sequences between amino acids 5 and 44 are required for interaction with menin and for the transformation of hematopoietic progenitors. Blocking the MLL-menin interaction by the expression of a dominant negative inhibitor composed of amino terminal MLL sequences down-regulates Meis1 expression and inhibits cell proliferation, suggesting that targeting this interaction may be an effective therapeutic strategy for leukemias with MLL rearrangements.

Original languageEnglish (US)
Pages (from-to)7275-7283
Number of pages9
JournalCancer Research
Volume67
Issue number15
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

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Leukemia
Lymphoid Leukemia
Myeloid Leukemia
Amino Acid Sequence
Proteins
Down-Regulation
Cell Proliferation
Gene Expression
Genes
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Interaction of MLL amino terminal sequences with menin is required for transformation. / Caslini, Corrado; Yang, Zhaohai; El-Osta, Mohamad; Milne, Thomas A.; Slany, Robert K.; Hess, Jay.

In: Cancer Research, Vol. 67, No. 15, 01.08.2007, p. 7275-7283.

Research output: Contribution to journalArticle

Caslini, Corrado ; Yang, Zhaohai ; El-Osta, Mohamad ; Milne, Thomas A. ; Slany, Robert K. ; Hess, Jay. / Interaction of MLL amino terminal sequences with menin is required for transformation. In: Cancer Research. 2007 ; Vol. 67, No. 15. pp. 7275-7283.
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