Imatinib-resistant CML cells have low ENT activity but maintain sensitivity to gemcitabine |
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Authors: | Leisewitz Andrea V Zimmerman Eric I Jones Shannon Z Yang Jing Graves Lee M |
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Institution: | Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599, USA. |
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Abstract: | Philadelphia chromosome-positive chronic myelogenus leukemia (CML) is widely treated with imatinib mesylate (imatinib), a potent inhibitor of the Bcr-Abl tyrosine kinase. However, resistance to this compound remains a concern. Current treatment approaches include combinations of imatinib with nucleoside analogs such as gemcitabine, which requires equilibrative nucleoside transporters (ENTs) for uptake, to overcome this resistance. Here we report that imatinib treatment decreased ENT1-dependent activity and mRNA expression. Although, imatinib-resistant cells showed decreased levels of both ENT1 and ENT2 activity and expression, these cells remained sensitive to gemcitabine, suggesting that nucleoside analogs can be used as adjunctive therapy. |
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