Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia
Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia
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DOI：
10.1158/0008-5472.can-03-1484
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发表时间：
2004-01-15
期刊：
影响因子：
11.2
通讯作者：
Talpaz, M
中科院分区：
文献类型：
--
作者：
Donato, NJ;Wu, JY;Talpaz, M
甲酸伊马替尼（Imatinib mesylate， IM）与BCR-ABL蛋白结合，抑制其激酶活性，有效控制由该激酶驱动的疾病。IM耐药与激酶突变或BCR-ABL表达增加有关。然而，疾病进展可能由其他机制介导，使肿瘤细胞不依赖于BCR-ABL。为了证明这一潜力，在BCR-ABL基因持续表达但BCR-ABL蛋白未检测到的慢性骨髓性白血病患者中发现了im耐药细胞。这些细胞对IM没有反应，并且获得了与bcr - abl无关的信号特征。一些患者的IM耐药可能是通过丧失激酶靶点依赖性介导的。
Imatinib mesylate (IM) binds to the BCR-ABL protein, inhibiting its kinase activity and effectively controlling diseases driven by this kinase. IM resistance has been associated with kinase mutations or increased BCR-ABL expression. However, disease progression may be mediated by other mechanisms that render tumor cells independent of BCR-ABL. To demonstrate this potential, IM-resistant cells were found in chronic myelogenous leukemia patients with continuous BCR-ABL gene expression but undetectable BCR-ABL protein expression. These cells were unresponsive to IM and acquired BCR-ABL-independent signaling characteristics. IM resistance in some patients may be mediated through loss of kinase target dependence.