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 during 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-inhibitable accumulation of DiOC(2) is robust and reproducible.
Marcelletti
John F
JF
Kanisa Pharmaceuticals, San Diego, CA, United States.
Multani
Pratik S
PS
Lancet
Jeffrey E
JE
Baer
Maria R
MR
Sikic
Branimir I
BI
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D001752:Blast Crisis; D003986:Dibenzocycloheptenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003986:Dibenzocycloheptenes; D005456:Fluorescent Dyes; D011804:Quinolines; C095179:zosuquidar trihydrochloride