Nilotinib significantly induces apoptosis in imatinib resistant K562 cells with wild-type BCR–ABL, as effectively as in parental sensitive counterparts

Abstract

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by high levels of immature white blood cells. CML is caused by the translocation between chromosomes 9 and 22 (which results in the formation of the Philadelphia chromosome) creating BCR–ABL fusion protein. Imatinib and nilotinib are chemotherapeutic drugs which specifically bind to the BCR–ABL and inhibit cancer cells. Nilotinib is more effective in this respect than imatinib. We have shown that nilotinib induces apoptosis in imatinib-resistant K562 CML cells which have the wild-type BCR–ABL fusion gene almost to the same extent as it does in the parental sensitive cells by the increase in caspase-3 enzyme activity and the decrease in mitochondrial membrane potential. This effect of nilotinib, even in low concentrations, may indicate the efficacy of the usage of nilotinib in imatinib-resistant CML with less risk of undesired cytotoxic effects in the remaining cells of the body.

Keywords:

• CML
• IMATINIB
• NILOTINIB
• DRUG RESISTANCE
• BCR-ABL