ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis

Abstract

Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR-ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.