Rousselot Philippe
Service d'hématologie-oncologie, hôpital André Mignot, 78157 Le Chesnay Cedex.
Rev Prat. 2005 Oct 15;55(15):1647-57.
Chronic myelogenous leukemia is the main diagnosis in case of primitive hyperleucocytosis ou thrombocytosis. The Philadelphia chromosome could be evidenced in the bone marrow by cytogenetic analysis or in the peripheral blood by amplification of the BCR-ABL fusion gene with RT-PCR. A new targeted therapy, imatinib mesylate (Gleevec), inhibits of the dysregulated kinase activity of BCR-ABL. A complete cytogenetic response defined by the absence of Ph+ chromosome in bone marrow is obtained in 85% of cases at the daily dosage of 400 mg. The response is then monitored by quantification of the BCR-ABL transcript. This apparent simple, orally available and well tolerated therapy need to be carefully monitored by real time quantitative PCR in highly specialized laboratories. Allogenic hematopoietic stem cell transplantation remains a curative approach in case of HLA identical donor and is proposed to young patients or in case of imatinib failure. A second generation of BCR-ABL inhibitors is currently in clinical trial.
慢性粒细胞白血病是原发性白细胞增多症或血小板增多症的主要诊断结果。通过细胞遗传学分析可在骨髓中发现费城染色体，或通过逆转录聚合酶链反应（RT-PCR）扩增BCR-ABL融合基因在外周血中发现该染色体。一种新的靶向治疗药物甲磺酸伊马替尼（格列卫）可抑制BCR-ABL失调的激酶活性。在每日剂量为400毫克时，85%的病例可获得由骨髓中无Ph+染色体所定义的完全细胞遗传学缓解。然后通过定量BCR-ABL转录本来监测缓解情况。这种看似简单、口服可用且耐受性良好的治疗方法需要在高度专业化的实验室中通过实时定量PCR进行仔细监测。对于有 HLA 匹配供体的情况，异基因造血干细胞移植仍然是一种治愈方法，并适用于年轻患者或伊马替尼治疗失败的情况。第二代BCR-ABL抑制剂目前正在进行临床试验。
