Flow cytometric determination of Src phosphorylation in pediatric patients treated with dasatinib

Guerrouahen, B. S.; Wieder, E.; Blanchard, E. G.; Lee, F. Y.; Aplenc, R.; Corey, S. J.

Pediatr Blood Cancer. 2009 Jun 2; 53(6):1132-5


Tyrosine kinase inhibitors, such as imatinib, have dramatically improved the outcomes for patients with selected cancers. For imatinib, western blotting of phospho-CrkL was an insensitive, indirect, and descriptive method to determine drug efficacy. Greater use of targeted therapies should involve more quantitative evaluation of the target's dose-inhibition. The Src/Abl kinase inhibitor dasatinib has recently been approved for use in Ph+ leukemias after failure with imatinib. Src family kinases (SFK) also play a critical role in nonhematologic cancers. We have developed a flow cytometric assay to measure SFK autophosphorylation levels in blood mononuclear cells and observed a direct correlation between its inhibition and patient dosage. This method provides a sensitive, quick, and quantitative tool to assess drug efficacy.

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