Department of Hematology/Oncology L. e A. Seràgnoli, University of Bologna, Bologna, Italy.
Blood. 2011 Aug 4;118(5):1208-15. doi: 10.1182/blood-2010-12-326405. Epub 2011 May 11.
Mutations in the Bcr-Abl kinase domain may cause, or contribute to, resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients. Recommendations aimed to rationalize the use of BCR-ABL mutation testing in chronic myeloid leukemia have been compiled by a panel of experts appointed by the European LeukemiaNet (ELN) and European Treatment and Outcome Study and are here reported. Based on a critical review of the literature and, whenever necessary, on panelists' experience, key issues were identified and discussed concerning: (1) when to perform mutation analysis, (2) how to perform it, and (3) how to translate results into clinical practice. In chronic phase patients receiving imatinib first-line, mutation analysis is recommended only in case of failure or suboptimal response according to the ELN criteria. In imatinib-resistant patients receiving an alternative TKI, mutation analysis is recommended in case of hematologic or cytogenetic failure as provisionally defined by the ELN. The recommended methodology is direct sequencing, although it may be preceded by screening with other techniques, such as denaturing-high performance liquid chromatography. In all the cases outlined within this abstract, a positive result is an indication for therapeutic change. Some specific mutations weigh on TKI selection.
Bcr-Abl 激酶结构域的突变可能导致或有助于慢性髓性白血病患者对酪氨酸激酶抑制剂（TKI）产生耐药性。由欧洲白血病网（ELN）和欧洲治疗与预后研究任命的专家组制定了旨在合理化慢性髓性白血病中 BCR-ABL 突变检测的使用的建议，并在此报告。基于对文献的批判性回顾，以及在必要时根据小组成员的经验，确定并讨论了关键问题，涉及：（1）何时进行突变分析，（2）如何进行，以及（3）如何将结果转化为临床实践。在接受伊马替尼一线治疗的慢性期患者中，根据 ELN 标准，仅在治疗失败或反应不佳的情况下才建议进行突变分析。在接受替代 TKI 的伊马替尼耐药患者中，如果根据 ELN 暂定定义发生血液学或细胞遗传学失败，则建议进行突变分析。推荐的方法是直接测序，尽管在某些情况下可以先用其他技术（如变性高效液相色谱）进行筛选。在本摘要中概述的所有情况下，阳性结果是治疗改变的指征。一些特定的突变会影响 TKI 的选择。
