Yeung Cecilia Ching Sze, Egan Daniel, Radich Jerald P
a Clinical Research Division , Fred Hutchinson Cancer Research Center Ringgold standard institution , Seattle , WA , USA.
b Pathology , University of Washington School of Medicine Ringgold standard institution , Seattle , WA , USA.
Expert Rev Mol Diagn. 2016 Oct;16(10):1083-1091. doi: 10.1080/14737159.2016.1227243. Epub 2016 Sep 6.
Fusion of BCR-ABL1 genes causes chronic myeloid leukemia (CML). As a reliable marker of disease burden, it also serves as the target of tyrosine kinase inhibitors (TKIs). New more sensitive molecular diagnostic tools for BCR-ABL1 can contribute to therapeutic decision-making, especially in considering drug discontinuation for patients enjoying prolonged deep molecular response. Areas covered: Several novel platforms are transforming CML molecular diagnostics to enable faster point-of-care devices, better understanding of clonal diversity and resistance mutations. Here, we review these molecular platforms, knowing implementation in other hematological malignancies will ensue. Expert commentary: Treatment with TKI in CML is the first example of a highly effective targeted therapy. Monitoring of BCR-ABL1 mRNA is standard in assessing disease burden being highly predictive of outcomes recommended by both European LeukemiaNet (ELN) and National Comprehensive Cancer Network (NCCN); however, studies has demonstrated poor adherence to these recommendations. In both clinical practice and assay performance, further optimizing of BCR-ABL1 monitoring can be envisioned including point-of-care methods for increased availability of rapid, standardized testing and increasingly sensitive molecular assays that allow for quantification of MRD and detecting resistance mutations.
BCR-ABL1基因融合导致慢性粒细胞白血病(CML)。作为疾病负担的可靠标志物,它也是酪氨酸激酶抑制剂(TKIs)的作用靶点。用于检测BCR-ABL1的更新颖、更灵敏的分子诊断工具有助于治疗决策,特别是在考虑为获得长期深度分子反应的患者停药时。涵盖领域:几种新型平台正在改变CML分子诊断,以实现更快的即时检测设备,更好地理解克隆多样性和耐药突变。在此,我们对这些分子平台进行综述,因为我们知道它们在其他血液系统恶性肿瘤中的应用也将随之而来。专家评论:CML中使用TKI治疗是高效靶向治疗的首个范例。监测BCR-ABL1 mRNA是评估疾病负担的标准方法,欧洲白血病网(ELN)和美国国立综合癌症网络(NCCN)均推荐其对预后具有高度预测性;然而,研究表明对这些建议的依从性较差。在临床实践和检测性能方面,均可设想进一步优化BCR-ABL1监测,包括采用即时检测方法以提高快速、标准化检测的可及性,以及采用日益灵敏的分子检测方法以实现微小残留病(MRD)定量分析和耐药突变检测。