Paul O'Gorman Leukaemia Research Centre, Section of Experimental Haematology, Faculty of Medicine, University of Glasgow, Gartnavel General Hospital, 1053 Great Western Road, Glasgow G12 0YN, United Kingdom.
Blood Rev. 2010 Jan;24(1):1-9. doi: 10.1016/j.blre.2009.11.002.
The introduction of imatinib, a tyrosine kinase inhibitor (TKI) that targets the BCR-ABL protein, has revolutionised the treatment of chronic myeloid leukaemia (CML), producing high rates of response that have been durable in many patients. However, because of intrinsic or acquired mechanisms of imatinib resistance, in addition to the persistence of leukaemic stem cells that are resistant to imatinib-induced apoptosis, imatinib treatment does not appear to be curative. Cytogenetic and molecular monitoring enable the identification of patients showing signs of treatment failure and can be used to guide choices regarding subsequent therapeutic options, including imatinib dose escalation, treatment with a secondary TKI or, in selected cases, allogeneic stem cell transplant (allo-SCT). Although these alternative therapies may overcome imatinib resistance, long-term remission or cure from CML is likely to require development of novel interventions that effectively eliminate CML stem cells (Ph+HSC).
伊马替尼的引入是一种酪氨酸激酶抑制剂（TKI），可靶向 BCR-ABL 蛋白，彻底改变了慢性髓性白血病（CML）的治疗方法，使许多患者获得了持久的高反应率。然而，由于伊马替尼耐药的内在或获得性机制，以及对伊马替尼诱导凋亡耐药的白血病干细胞的持续存在，伊马替尼治疗似乎不能治愈。细胞遗传学和分子监测可识别出出现治疗失败迹象的患者，并可用于指导后续治疗选择，包括伊马替尼剂量升级、使用二线 TKI 治疗或在选定情况下进行异基因造血干细胞移植（allo-SCT）。虽然这些替代疗法可能克服伊马替尼耐药性，但从 CML 中获得长期缓解或治愈可能需要开发新的干预措施，这些措施可有效消除 CML 干细胞（Ph+HSC）。
