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

Bella S. Guerrouahen; Eric Wieder; Elisabeth G. Blanchard; Francis Y. Lee; Richard Aplenc; Seth J. Corey

doi:10.1002/pbc.22083

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

Bella S. Guerrouahen, Eric Wieder, Elisabeth G. Blanchard, Francis Y. Lee, Richard Aplenc, Seth J. Corey

Medicine

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1132-1135
Number of pages	4
Journal	Pediatric Blood and Cancer
Volume	53
Issue number	6
DOIs	https://doi.org/10.1002/pbc.22083
State	Published - 2009

Keywords

Dasatinib
Phase I
Src kinases
Tyrosine kinase inhibitor

ASJC Scopus subject areas

Oncology
Pediatrics, Perinatology, and Child Health
Hematology

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abstract = "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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AU - Wieder, Eric

AU - Blanchard, Elisabeth G.

AU - Lee, Francis Y.

AU - Aplenc, Richard

AU - Corey, Seth J.

PY - 2009

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