Imatinib failure and response to dasatinib in a patient with chronic myeloid leukemia in blast crisis and a novel, nine-nucleotide BCR-ABL insertion mutation

摘要

In chronic phase chronic myeloid leukemia (CML), the BCR-ABL kinase inhibitor imatinib leads to complete cytogenetic responses in the majority of cases. Resistance towards imatinib is associated with BCR-ABL kinase domain mutations, leading to structural changes that prevent imatinib from binding. 1 In cases of failure towards imatinib treatment, second generation BCR-ABL kinase inhibitors such as dasatinib or nilotinib have demonstrated activity in CML. 2 Both drugs are capable of suppressing imatinib-resistant, mutant forms of BCR-ABL. 3 Most of the mutations in the BCR-ABL gene mediating inhibitor resistance are point mutations, replacing single nucleotides.