文章：

靶向RNA测序在白血病诊断与管理中的真实世界临床应用价值

Real-World Clinical Utility of Targeted RNA Sequencing in Leukemia Diagnosis and Management

原文发布日期：5 July 2024

DOI: 10.3390/cancers16132467

类型: Article

开放获取: 是

英文摘要：

Gene fusions are key drivers in acute leukemia, impacting diagnosis and treatment decisions. We analyzed 264 leukemia patients using targeted RNA sequencing with conventional karyotyping and reverse transcription polymerase chain reaction (RT-PCR). Leukemic fusions were detected in 127 patients (48.1%). The new guidelines introduced additional diagnostic criteria, expanding the spectrum of gene fusions. We discovered three novel fusions (RUNX1::DOPEY2,RUNX1::MACROD2, andZCCHC7::LRP1B). We analyzed recurrent breakpoints for theKMT2AandNUP98rearrangements. Targeted RNA sequencing showed consistent results with RT-PCR in all tested samples. However, when compared to conventional karyotyping, we observed an 83.3% concordance rate, with 29 cases found only in targeted RNA sequencing, 7 cases with discordant results, and 5 cases found only in conventional karyotyping. For the five cases where known leukemic gene rearrangements were suspected only in conventional karyotyping, we conducted additional messenger RNA sequencing in four cases and proved no pathogenic gene rearrangements. Targeted RNA sequencing proved advantageous for the rapid and accurate interpretation of gene rearrangements. The concurrent use of multiple methods was essential for a comprehensive evaluation. Comprehensive molecular analysis enhances our understanding of leukemia’s genetic basis, aiding diagnosis and classification. Advanced molecular techniques improve clinical decision-making, offering potential benefits.

摘要翻译： 

基因融合是急性白血病的关键驱动因素，对诊断和治疗决策具有重要影响。我们采用靶向RNA测序结合常规核型分析和逆转录聚合酶链反应（RT-PCR）对264例白血病患者进行了分析。在127例患者（48.1%）中检测到白血病相关基因融合。新指南引入了额外的诊断标准，拓展了基因融合的检测范围。我们发现了三种新型融合基因（RUNX1::DOPEY2、RUNX1::MACROD2和ZCCHC7::LRP1B）。针对KMT2A和NUP98重排，我们分析了其反复出现的断裂点。在所有检测样本中，靶向RNA测序与RT-PCR结果一致。然而，与常规核型分析相比，两者的一致性率为83.3%，其中29例仅在靶向RNA测序中检出，7例结果不一致，5例仅在常规核型分析中发现。对于常规核型分析疑似存在已知白血病基因重排的5例病例，我们对其中4例进行了额外信使RNA测序，证实不存在致病性基因重排。靶向RNA测序在快速准确解析基因重排方面显示出优势。多种方法的联合使用对于全面评估至关重要。综合分子分析深化了我们对白血病遗传基础的理解，有助于疾病诊断和分型。先进分子技术的应用提升了临床决策水平，具有潜在临床获益。

原文链接：

Real-World Clinical Utility of Targeted RNA Sequencing in Leukemia Diagnosis and Management