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Bioessays. 2012 Sep;34(9):771-80. doi: 10.1002/bies.201200007. Epub 2012 Jul 24.

Menin as a hub controlling mixed lineage leukemia.

Author information

  • 1Department of Cancer Biology, Abramson Family Cancer Research Institute, Abramson Cancer Center, The University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.

Abstract

Mixed lineage leukemia (MLL) fusion protein (FP)-induced acute leukemia is highly aggressive and often refractory to therapy. Recent progress in the field has unraveled novel mechanisms and targets to combat this disease. Menin, a nuclear protein, interacts with wild-type (WT) MLL, MLL-FPs, and other partners such as the chromatin-associated protein LEDGF and the transcription factor C-Myb to promote leukemogenesis. The newly solved co-crystal structure illustrating the menin-MLL interaction, coupled with the role of menin in recruiting both WT MLL and MLL-FPs to target genes, highlights menin as a scaffold protein and a central hub controlling this type of leukemia. The menin/WT MLL/MLL-FP hub may also cooperate with several signaling pathways, including Wnt, GSK3, and bromodomain-containing Brd4-related pathways to sustain MLL-FP-induced leukemogenesis, revealing new therapeutic targets to improve the treatment of MLL-FP leukemias.

Copyright © 2012 WILEY Periodicals, Inc.

PMID:
22829075
[PubMed - indexed for MEDLINE]
PMCID:
PMC3536020
Free PMC Article

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