文章：

基于风险的白血病细胞遗传学和多重分子方法分类：来自多中心验证研究的结果

Risk-based classification of leukemia by cytogenetic and multiplex molecular methods: results from a multicenter validation study

原文发布日期：2012-07-13

DOI: 10.1038/bcj.2012.24

类型: Original Article

开放获取: 是

英文摘要：

Modern management of leukemia and selection of optimal treatment approaches entails the analysis of multiple recurrent cytogenetic abnormalities with independent diagnostic or prognostic value. We report the first multicenter validation of a multiplex molecular assay for 12 relevant fusion transcripts relative to cytogenetic methods. Performance was evaluated using a set of 280 adult and pediatric acute or chronic leukemias representative of the variety of presentations and pre-analytical parameters encountered in the clinical setting. The positive, negative and overall agreements were >98.5% with high concordance at each of the four sites. Positive detection of cases with low blast count or at relapse was consistent with a method sensitivity of 1%. There was 98.7% qualitative agreement with independent reference molecular tests. Apparent false negatives corresponded to rare alternative splicing isoforms not included in the panel. We further demonstrate that clinical sensitivity can be increased by adding those rare variants and other relevant transcripts or submicroscopic abnormalities. We conclude that multiplex RT-PCR followed by liquid bead array detection is a rapid and flexible method attuned to the clinical laboratory workflow, complementing standard cytogenetic methods and generating additional information valuable for the accurate diagnosis, prognosis and subsequent molecular monitoring of leukemia.

摘要翻译： 

白血病现代治疗方案及最佳治疗策略的选择，需对多种具有独立诊断或预后价值的复发性细胞遗传学异常进行分析。我们首次就12种相关融合转录本的多重分子检测与细胞遗传学方法开展多中心验证。采用280例成人和儿童急慢性白血病样本进行评估，这些样本充分体现了临床实践中各种临床表现及分析前参数的多样性。阳性符合率、阴性符合率和总符合率均超过98.5%，且四个研究中心均呈现高度一致性。对低原始细胞计数或复发病例的阳性检测结果证实该方法灵敏度达1%。与独立参考分子检测的定性符合率为98.7%。表面假阴性结果对应于检测组合未涵盖的罕见选择性剪接异构体。我们进一步证明，通过添加这些罕见变异及其他相关转录本或亚显微异常，可提高临床灵敏度。本研究得出结论：液相芯片阵列检测结合多重RT-PCR是一种快速灵活的方法，能有效契合临床实验室工作流程，既可补充标准细胞遗传学方法，又能为白血病的精准诊断、预后判断及后续分子监测提供宝贵信息。

原文链接：

Risk-based classification of leukemia by cytogenetic and multiplex molecular methods: results from a multicenter validation study