New data, generated by a team of researchers, at the University of Pennsylvania School of Medicine, Philadelphia, and Brigham and Women's Hospital, Boston, have now indicated that only uncommon T-ALL-associated NOTCH1 mutations have the ability to induce cells to become leukemic in mice (these uncommon mutations generated Notch1 proteins with far greater increased activity than the Notch1 proteins generated by the more common mutations).
However, although the more than common mutations were non themselves able to cause cells to become leukemic in mice, they were able to accelerate the onset of leukemia induced by other genetic mutations.
The authors therefore indicate that all T-ALL leukemic cells with mutations in the NOTCH1 gene ar "addicted" to Notch and that this study provides support for the rating of Notch signaling pathway inhibitors as a treatment for cancer of the blood.
"Leukemia-associated NOTCH1 alleles ar weak tumour initiators just accelerate K-ras-initiated leukemia"
Mark Y. Chiang, Lanwei Xu, Olga Shestova, Gavin Histen, Sarah L'Heureux, Candice Romany, M. Eden Childs, Phyllis A. Gimotty, Jon C. Aster and Warren S. Pear
J. Clin. Invest. doi:10.1172/JCI35090
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The Journal of Clinical Investigation (JCI) is the publication of the American Society for Clinical Investigation, an honor society of physician-scientists.
www.jci.org
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