Mechanisms of resistance to BCR-ABL TKIs and the therapeutic strategies: A review.

BCR-ABL caused by the translocation of t(9,22) with elevated tyrosine-kinase activity could induce leukemia in mice, which established BCR-ABL as the molecular pathogenic event in CML (Chronic myeloid leukemia). In recent years, a variety of tyrosine kinase inhibitors (TKIs) targeting at BCR-ABL specifically and effectively have been developed, which has fundamentally promoted the treatment of CML. However, the efficacy of TKIs was limited by its resistance induced by the development of kinase domain mutations and other mechanisms illustrated. In this review, we summarized BCR-ABL inhibitors approved by Food and Drug Administration (FAD), with the same concerns focus on the resistant mechanisms of BCR-ABL inhibitors and therapeutic resistant strategies.