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 L. Hess

Research output: Contribution to journalArticle

96 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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