Prospects & Overviews
Menin as a hub controlling mixed lineage leukemia
Article first published online: 24 JUL 2012
Copyright © 2012 WILEY Periodicals, Inc.
Volume 34, Issue 9, pages 771–780, September 2012
How to Cite
Thiel, A. T., Huang, J., Lei, M. and Hua, X. (2012), Menin as a hub controlling mixed lineage leukemia. Bioessays, 34: 771–780. doi: 10.1002/bies.201200007
- Issue published online: 14 AUG 2012
- Article first published online: 24 JUL 2012
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.