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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.

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


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.

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