Imatinib-resistant CML cells have low ENT activity but maintain sensitivity to gemcitabine.
Nucleosides Nucleotides Nucleic Acids
; 27(6): 779-86, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18600540
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Pirimidinas
/
Resistencia a Medicamentos Antineoplásicos
/
Proteínas de Transporte de Nucleosídeo Equilibrativas
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Desoxicitidina
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article