O'Dwyer Michael E, Mauro Michael J, Druker Brian J
Leukemia Center, Oregon Health & Science University Cancer Institute, Portland, Oregon, USA.
Cancer Invest. 2003 Jun;21(3):429-38. doi: 10.1081/cnv-120018235.
Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder that progresses through distinct phases as the malignant clone progressively loses the capacity for terminal differentiation. It is characterized by the (9;22) translocation and resultant production of the Bcr-Abl tyrosine kinase. Bcr-Abl functions as a constitutively activated tyrosine kinase, and this kinase activity is absolutely required for the transforming function of the Bcr-Abl protein. In preclinical studies, STI571 (Gleevec, imatinib mesylate), a Bcr-Abl tyrosine kinase inhibitor, specifically inhibited the proliferation of Bcr-Abl-expressing cells in vitro and in vivo. STI571 has shown remarkable results in all phases of CML. Although responses are seen in all phases of the disease, durable responses are most common in earlier stage patients. Thus, STI571 has emerged as a paradigm for gene product targeted therapy, offering expanded treatment options for patients with CML.
慢性粒细胞白血病（CML）是一种克隆性造血干细胞疾病，随着恶性克隆逐渐丧失终末分化能力，疾病会经历不同阶段。其特征是存在（9；22）易位并产生Bcr-Abl酪氨酸激酶。Bcr-Abl作为一种组成型激活的酪氨酸激酶发挥作用，这种激酶活性对于Bcr-Abl蛋白的转化功能是绝对必需的。在临床前研究中，Bcr-Abl酪氨酸激酶抑制剂STI571（格列卫，甲磺酸伊马替尼）在体外和体内均能特异性抑制表达Bcr-Abl的细胞增殖。STI571在CML的各个阶段均显示出显著疗效。尽管在疾病的各个阶段都能看到反应，但持久反应在早期患者中最为常见。因此，STI571已成为基因产物靶向治疗的典范，为CML患者提供了更多的治疗选择。
