Leukemic blast and natural killer cell P-glycoprotein function and inhibition in a clinical trial of zosuquidar infusion in acute myeloid leukemia

A bioassay was developed to assess P-glycoprotein (P-gp) function of peripheral blood natural killer (NK) cells and AML blasts doting zosuquidar infusion. Cells were incubated with the fluorescent dye DiOC(2) (3) in the presence and absence Of zosuquidar, and dye accumulation measured by flow cytometry. The assay performance was assessed Using NK cells and the P-gp-positive K562/R7 cell line, and then utilized to determine the function of P-gp and its inhibition by zosuquidar in AML blasts and NK cells from patients enrolled in a Phase I trial. The assay of zosuquidar-inhitable accumulation of DiOC(2) is robust and reproducible. (C) 2008 Elsevier Ltd. All rights reserved.