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The introduction of selective tyrosine-kinase inhibitors (TKIs) for the treatment of chronic myeloid leukaemia has changed patient outcome and, consequently, management of this disease. Imatinib is now the treatment of choice for most newly diagnosed patients. Excellent responses, in terms of symptom control and haematological parameters, are usually obtained. However, failure to completely eradicate leukaemic cells and the escape of these cells from previous control has led to an intensive search for the mechanisms of resistance and subsequent treatments by which to overcome this resistance. Up to now, there has been considerable focus on the role of ABL-kinase-domain mutations as mediators of resistance to imatinib, thereby encouraging the development of a second generation of TKIs capable of inhibiting these mutant proteins. However, studies have increasingly shown that these mutations do not …