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伊马替尼(Imatinib,STI571)是一种特异性强,高效酪氨酸激酶抑制剂。临床试验表明治疗慢性粒细胞白血病(CML)的疗效是干扰素的10倍。但是,该药在晚期或急变期 CML 平均使用10．5周后疗效明显下降,提示这些患者使用该药后发生了耐药。其发生机制可能为 BCR-ABL 酪氨酸激酶蛋白的浓度增加,mRNA 的表达水平的上调,基因扩增或突变,多耐药基因1(multi drug resistance,mdrl)及其产物 P-gp 的过表达及其它机制。发生耐药后的主要对策为联合传统化疗药物和其他信号转导抑制剂或加大伊马替尼的剂量。
Imatinib (STI571) is a potent and potent tyrosine kinase inhibitor. Clinical trials show that treatment of chronic myeloid leukemia (CML) is 10 times more effective than interferon. However, the mean reduction in efficacy of CML after 10.5 weeks of treatment in advanced or blast phase CML suggests that these patients developed resistance after using the drug. The mechanism may be the increase of the concentration of BCR-ABL tyrosine kinase protein, the up-regulation of mRNA expression, gene amplification or mutation, multi-drug resistance (mdrl) and the product P-gp Expression and other mechanisms. After the emergence of drug resistance is the main countermeasure combined with traditional chemotherapy drugs and other signal transduction inhibitors or increase the dose of imatinib.