Alvarez Ricardo H, Kantarjian Hagop, Cortes Jorge E
Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
Semin Hematol. 2007 Jan;44(1 Suppl 1):S4-14. doi: 10.1053/j.seminhematol.2006.12.007.
Chronic myelogenous leukemia (CML) results from the neoplastic transformation of primitive hematopoietic stem cells, and has been classified as a myeloproliferative disorder. The hallmark of CML is the presence of a balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11.2), which is known as the Philadelphia (Ph) chromosome. This translocation results in the formation of the bcr-abl fusion gene, which, in turn, is translated into a chimeric Bcr-Abl protein with deregulated tyrosine kinase activity. Constitutive Bcr-Abl expression has been shown to be necessary and sufficient for the transformed phenotype of CML cells. CML is unique among human cancers in that a single genetic defect, the Ph chromosome, is responsible for the transformed phenotype. Since this discovery more than 40 years ago, our understanding of the clinical course, therapy, and prognosis of patients with CML has changed significantly. These changes have culminated in the emergence of imatinib, the first rationally designed, molecularly targeted therapy for human malignancy. In this review, the authors describe the molecular biology of CML and the development of imatinib as a therapeutic agent for the treatment of CML.
慢性粒细胞白血病（CML）源于原始造血干细胞的肿瘤性转化，已被归类为骨髓增殖性疾病。CML的标志是9号和22号染色体长臂之间存在平衡易位，即t(9;22)(q34;q11.2)，这被称为费城（Ph）染色体。这种易位导致bcr-abl融合基因的形成，进而被翻译成具有失调酪氨酸激酶活性的嵌合Bcr-Abl蛋白。组成型Bcr-Abl表达已被证明对于CML细胞的转化表型是必要且充分的。CML在人类癌症中是独特的，因为单一的基因缺陷，即Ph染色体，导致了转化表型。自40多年前这一发现以来，我们对CML患者的临床病程、治疗和预后的理解发生了显著变化。这些变化最终促成了伊马替尼的出现，这是第一种针对人类恶性肿瘤的合理设计的分子靶向治疗药物。在这篇综述中，作者描述了CML的分子生物学以及伊马替尼作为治疗CML的治疗药物的发展。
