慢性粒细胞白血病靶向治疗药物实验研究进展

Experimental Advance of Targeted Medicines for Chronic Myeloid Leukemia——Review

慢性粒细胞白血病(CML)是一种起源于骨髓内异常多能干细胞的骨髓增殖性疾病,以持续表达bcr-abl融合基因为特征。这段融合基因的翻译产物Bcr-Abl蛋白具有增高的蛋白酪氨酸激酶活性,可以激活一系列下游信号传导通路而导致CML的发生。尽管靶向治疗药物蛋白酪氨酸激酶抑制剂甲磺酸伊马替尼(imatinib,IM)的临床应用使几乎所有CML慢性期的患者达到完全血液学缓解和其中90%的早期患者达到完全细胞遗传学缓解,然而临床实践和实验研究发现,有些患者在临床治疗过程中发生了IM耐药或原发性耐药,迫使人们着眼于新型制剂的研究和与IM联合用药的研究,以期获得更好的疗效。本文就近年来发展的针对CML的新型靶向治疗药物的实验研究进展加以综述。

Chronic myelogenous leukemia （CML） is a myeloproliferative disorder from hematopoietic stem cell disorder characterized by the consecutive expression of bcr-ab1 gene, and the translation product of which has enhanced tyrosine kinase activity and can activate a series of downstream signal transduction proteins and results in the occurence of CML. Although the application of imatinib （IM） makes nearly all patients with CML in chronic phase achieve a complete hematologic remission, and 90% of those treated in the early chronic phase achieve a complete cytogenetic remission, but the development of resistance to IM in the course of treatment and even in the beginning of the treatment forced people to develop new agents and to combine the new agents with IM in order to achieve better therapcutic result. This article reviews the experimental advances of targeted therapeutics in CML recent years,