Our genes are arranged on 23 pairs of chromosomes. Chromosomal abnormalities that occur when nonmatching pairs of chromosomes swap genetic information are known as chromosomal translocations. Chromosomal translocations are the cause of several forms of leukemia, as they can result in dysregulation of genes that cause cancer.
The gene MLL is often inappropriately regulated in acute leukemias caused by chromosomal translocation, and Alan Gewirtz and colleagues, at the University of Pennsylvania School of Medicine, Philadelphia, have now identified a molecular pathway that is important for inducing MLL-associated leukemia formation.
In the study, the authors find that in human leukemia cells the protein c-myb binds to MLL via the protein menin and that this is important for MLL to drive mouse blood cells to become leukemic. Further analysis indicated that the c-myb/menin/MLL complex induced changes to genomic structure, leading to changes in gene expression. The authors suggest that deeper understanding of the gene networks regulated by the c-myb/menin/MLL complex might provide new drug targets for treatments for acute leukemia.
The research appears in the Journal of Clinical Investigation.
- Shenghao Jin, Huiwu Zhao, Yan Yi, Yuji Nakata, Anna Kalota and Alan M. Gewirtz. c-Myb binds MLL through menin in human leukemia cells and is an important driver of MLL-associated leukemogenesis. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI38030
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