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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1132-1135
Number of pages4
JournalPediatric Blood and Cancer
Volume53
Issue number6
DOIs
StatePublished - 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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