Department of Hematology/Oncology L. e A. Seragnoli, S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138, University of Bologna, Bologna, Italy.
Pharmacogenomics. 2012 Aug;13(11):1271-84. doi: 10.2217/pgs.12.103.
Over the last decade, the treatment of chronic myeloid leukemia has progressed tremendously. The first-generation tyrosine kinase inhibitor imatinib is now flanked by two second-generation molecules, dasatinib and nilotinib - and others are in advanced clinical development. One of the reasons for such intensive research on novel compounds is the problem of resistance, that is thought to be caused, in a proportion of cases, by point mutations in Bcr-Abl. In this article, the authors review how the biological and clinical relevance of Bcr-Abl mutations has evolved in parallel with the availability of more and more therapeutic options. The authors also discuss the practical relevance of Bcr-Abl mutation analysis and how this tool should best be integrated in the optimal clinical management of chronic myeloid leukemia patients.
在过去的十年中，慢性髓性白血病的治疗取得了巨大的进展。第一代酪氨酸激酶抑制剂伊马替尼现在有两种第二代药物达沙替尼和尼罗替尼作为辅助药物——还有其他药物正在进行临床开发。对新型化合物进行如此密集研究的原因之一是耐药性问题，耐药性据认为在一定比例的病例中是由 Bcr-Abl 中的点突变引起的。在本文中，作者回顾了 Bcr-Abl 突变的生物学和临床相关性如何与越来越多的治疗选择的出现同步发展。作者还讨论了 Bcr-Abl 突变分析的实际意义以及如何将该工具最佳地整合到慢性髓性白血病患者的最佳临床管理中。
