Mechanisms of Primary and Secondary Resistance to Imatinib in Chronic Myeloid Leukemia
Mechanisms of Primary and Secondary Resistance to Imatinib in Chronic Myeloid Leukemia
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DOI：
10.1177/107327480901600204
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发表时间：
2009-04-01
期刊：
影响因子：
2.6
通讯作者：
Cortes, Jorge E.
中科院分区：
文献类型：
--
作者：
Quintes-Cardama, Alfonso;Kantarjian, Hagop M.;Cortes, Jorge E.
背景：虽然绝大多数慢性粒细胞白血病(CML)患者对酪氨酸激酶抑制剂甲磺酸伊马替尼(TKI)有反应，但在治疗过程中或在治疗过程中可能会出现耐药。方法：作者综述了已知的对伊马替尼和其他用于治疗慢性髓系白血病的TKI的耐药机制。结果：在伊马替尼耐药病例中，bcr-abli的激酶域突变占30%~40%。其他机制包括bcr-abli扩增，SRC蛋白家族的过度表达，以及药代动力学和药效学因素。结论：尽管并不是所有的耐药机制都被识别和理解，但基于已知机制的几种药物已经设计和开发，并开始临床试验。
Background: Although the vast majority of patients with chronic myeloid leukemia (CML) respond to the tyrosine kinase inhibitor (TKI) imatinib mesylate, resistance might occur de novo or during treatment.Methods: The authors reviewed the known mechanisms of primary and secondary resistance to imatinib and other TKIs used in the management of CML.Results: Mutations within the kinase domain of BCR-ABLI account for 30% to 40% of cases of imatinib resistance. Other mechanisms include BCR-ABLI amplification, overexpression of the SRC family of kinases, and pharmacokinetic and pharmacodynamic factors.Conclusions: Although not all resistance mechanisms have been identified and understood, several agents based on the known mechanisms have already been designed and developed and are beginning clinical trials.