Fine-tuning targeted therapy of CML.

摘要

Imatinib, the first approved BCR-ABL-selective tyrosine kinase inhibitor, was rapidly established as the preferred frontline therapy for newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) on the basis of its ability to achieve a complete cytogenetic response (CCyR; denned as no detectable Philadelphia chromosome in at least 20 evaluable bone marrow meta-phases) in the majority of cases. Unfortunately, it is estimated that imatinib fails to achieve CCyR within 18 months in approximately 25% of patients. These persons are at higher risk for the development of progressive disease, which has been most commonly associated with the development of drug-resistant BCR-ABL kinase domain mutations