Swords Ronan, Alvarado Yesid, Giles Francis
Department of Hematology, University College Hospital Galway, Galway, Ireland.
Clin Lymphoma Myeloma. 2007 Mar;7 Suppl 3:S113-9. doi: 10.3816/clm.2007.s.011.
Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome, which is associated with a balanced translocation involving chromosomes 9 and 22 to produce a fusion gene (bcr-abl) that gives rise to a constitutively activated Abl tyrosine kinase. This kinase led to the discovery of several small-molecule inhibitors, imatinib being the first and most successful of these. Resistance to imatinib results in some patients from Abl kinase point mutations. Overcoming imatinib resistance represents one of the biggest challenges facing clinicians in the modern management of CML. In this review, we discuss the current understanding of CML pathophysiology and mechanisms of imatinib resistance and how advancing this knowledge has led to the design of novel therapies in the area of blastic phase CML and Philadelphia chromosome-positive acute lymphoblastic leukemia with previous imatinib failure.
慢性髓性白血病（CML）的特征是存在费城染色体，该染色体与涉及9号和22号染色体的平衡易位相关，产生一个融合基因（bcr-abl），该基因会产生持续激活的Abl酪氨酸激酶。这种激酶促使发现了几种小分子抑制剂，伊马替尼是其中第一种也是最成功的一种。一些患者对伊马替尼的耐药性源于Abl激酶点突变。克服伊马替尼耐药性是现代CML治疗中临床医生面临的最大挑战之一。在本综述中，我们讨论了目前对CML病理生理学和伊马替尼耐药机制的理解，以及对这些知识的深入了解如何促成了在急变期CML和既往伊马替尼治疗失败的费城染色体阳性急性淋巴细胞白血病领域设计新的治疗方法。
