Abstract
We studied the effects of Lyn ablation on the survival of drug-resistant chronic myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+)) blasts by 80–95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent apoptosis, whereas normal cells remained viable. This increased dependence on Lyn signaling for BCR-ABL1(+) blast survival provides the basis for rational treatment of drug-resistant CML blast crisis, particularly when lymphoid in nature.
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Acknowledgements
We thank D. Linnekin for providing us with Lyn cDNA. These studies were supported by grants from the Doris Duke Charitable Foundation (DDCF) to A.M.G., 1R01CA101859-01 (A.M.G.) and RO1CA90833 (S.G.E.) from the US National Institutes of Health, a SCOR grant from the Leukemia and Lymphoma Society (A.M.G. and S.G.E.). A. M. Gewirtz is a Distinguished Clinical Scientist of the DDCF.
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Ptasznik, A., Nakata, Y., Kalota, A. et al. Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells. Nat Med 10, 1187–1189 (2004). https://doi.org/10.1038/nm1127
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DOI: https://doi.org/10.1038/nm1127
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