Some cases of a form of leukemia known as pre–B cell acute lymphoblastic leukemia (pre–B-ALL) are caused by a genetic event that leads to the generation of a rogue chromosome known as the Philadelphia (Ph) chomosome, and individuals with Ph+ pre–B-ALL tend to have a poor outlook. As current treatments for Ph+ pre–B-ALL are not very effective, researchers are looking for new drugs to combat this disease.
And now, David Fruman and colleagues, at the University of California, at Irvine, have generated data in mice and human cells that might provide insight into a new molecule to target in this clinical setting.
In the study, deletion of two genes responsible for generating a molecule known as PI3K prevented the development of disease in a mouse model of Ph+ pre–B-ALL. Consistent with an important role for PI3K in the development of Ph+ pre–B-ALL, a drug that inhibits PI3K as well as another signaling molecule known as mTOR suppressed the growth of mouse B-ALL and human Ph+ ALL leukemia cells in vitro.
The authors therefore suggest that targeting PI3K, either alone or together with mTOR, might prove beneficial to individuals with of Ph+ pre–B-ALL.
- Kharas et al. Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL leukemia cells
. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI33337
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