Donato Nicholas J, Wu Ji Y, Stapley Jonathan, Lin Hui, Arlinghaus Ralph, Aggarwal Bharat B, Shishodia Shishir, Albitar Maher, Hayes Kimberly, Kantarjian Hagop, Talpaz Moshe
Department of Bioimmunotherapy, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Res. 2004 Jan 15;64(2):672-7. doi: 10.1158/0008-5472.can-03-1484.
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.
甲磺酸伊马替尼（IM）与BCR-ABL蛋白结合，抑制其激酶活性，并有效控制由该激酶驱动的疾病。IM耐药性与激酶突变或BCR-ABL表达增加有关。然而，疾病进展可能由其他机制介导，使肿瘤细胞独立于BCR-ABL。为了证明这种可能性，在持续表达BCR-ABL基因但检测不到BCR-ABL蛋白表达的慢性髓性白血病患者中发现了IM耐药细胞。这些细胞对IM无反应，并获得了不依赖BCR-ABL的信号特征。一些患者的IM耐药性可能通过激酶靶点依赖性的丧失来介导。
