虽然伊马替尼的疗效已经彻底改变了慢性粒细胞白血病（CML）的治疗，但它仍然不是一个治愈所有。在CML患者的一小部分患者中，既有最初的耐药性，也有因选择而获得的耐药性。ABL激酶域突变E255K被证明是一种对伊马替尼产生耐药性的突变。针对BCR-ABL的第二代TKI（达沙替尼和尼洛替尼）在治疗耐药病例方面显示出疗效。
While the efficacy of imatinib has revolutionized chronic myelogenous leukemia (CML) treatment, it is still not a cure-all. Both initial resistance and acquired resistance as a result of selection have been seen in a small subset of CML patients. The ABL kinase domain mutation E255K has been shown to be one such mutation that confers resistance to imatinib. Second generation TKI's (dasatinib and nilotinib) specific to BCR-ABL have shown efficacy in treating resistant cases.