Es nucleoside transporter content of acute leukemia cells: Role in cell sensitivity to cytarabine (araC)

Nucleoside analogs are important components of treatment regimens for acute leukemia in adults. Plasma membrane permeation of the nucleoside analog mo lecules, the initial event in the cellular conversion of nucleosides to act ive agents, is mediated by nucleoside-specific membrane transporters. The w idely-expressed es nucleoside transporter accepts as substrates diverse nuc leoside analogs, including cytarabine (araC), 2-chlorodeoxyadenosine, and f ludarabine. The cellular content of es transporter sites has been measured in blasts from patients with acute lymphoblastic leukemia and acute myeloge nous leukemia, by a sensitive, quantitative flow cytometry assay that emplo ys the tightly-bound es ligand, SAENTA fluorescein. Values for es transport er expression varied ten-fold among samples from patients with acute myelog enous leukemia. In this article, we review current findings that document, in confocal fluorescence microscopy images and in flow cytometry assays of SAENTA fluorescein-stained cells, the patient-to-patient variance of es tra nsporter expression in leukemic blasts from patients, Our data show a corre lation between the expression of es transporters and the in vitro sensitivi ty to nucleoside drugs of blasts from acute leukemia patients, These findin gs show that the flow cytometry assay of es expression provides a facile me ans of predicting resistance of leukemia cells to the cytotoxicity of araC and other nucleosides.