Wang, Liya
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences
Abstract
Background and Objectives. Clofarabine (CADdA), one of the newer nucleoside drugs is undergoing a phase II clinical trial for the treatment of pediatric refractory/relapsed acute myeloid and lymphocytic leukemia. Although CAFdA is structurally similar to the clinically established analogs fludarabine and cladribine (CdA), its metabolism and mechanism of actions are significantly different. The present study investigates the in vitro cytotoxicity of CAFdA and CdA in mononuclear cells isolated from 52 patients with chronic lymphocytic (CLL) and acute myeloid leukemia (AML). Design and methods. We incubated the leukemic cells with drugs for 48 hours and cytotoxicity was then evaluated by the MTT dye assay. We also determined the levels of deoxycytidine and deoxyguanosine kinase with radio-chemical substrate-based assays and used a high performance liquid chromatographic method to measure cellular nucleotides in leukemia cells after 2 hours' incubation. Results. Using equimolar concentrations of CAFdA and CdA, the in vitro cytotoxicity for the population was significantly higher with CAFdA than with CdA (median EC50 for CAFdA 0.12 muM and for CdA 0.15 muM, p
Keywords
cladribine; clofarabine; deoxycytidine kinase; deoxyguanosine kinase; leukemia; in vitro cytotoxicity
Published in
Haematologica
2003, volume: 88, number: 3, pages: 324-332
Publisher: FERRATA STORTI FOUNDATION
SLU Authors
Permanent link to this page (URI)
https://res.slu.se/id/publ/1810