Nat Commun:用临床转录组方法对急性髓性白血病患者进行分层和治疗选择 

2021-05-04 haibei MedSci原创

最近,研究人员开发并验证了一种基于临床转录组的检测方法,用于急性骨髓性白血病(AML)的分层。

骨髓性恶性肿瘤由一组相关的造血干细胞/祖细胞癌症组成,包括急性骨髓性白血病(AML)和骨髓增生异常综合征(MDS)。令人沮丧的是,几十年来,60岁以上的AML患者的预后没有实质性的改善。这种缺乏进展的情况表明,我们急需改进诊断方法、临床评估和治疗策略,所有这些都需要更好地了解这些疾病的遗传基础。

目前,AML的临床诊断和风险分层依赖于结构性基因组改变的细胞遗传学筛查,以及基于序列的预后和预测性基因变异的定向筛查。然而,约50%的患者被分层为中度风险组,仍然难以分配到适当的巩固治疗方案,这说明我们需要改进AML患者的分层。

随着更多与临床相关的骨髓性恶性肿瘤的基因组特征被发现,有针对性的临床基因测试显然不足以进行风险分层。最近,研究人员开发并验证了一种基于临床转录组的检测方法,用于急性骨髓性白血病(AML)的分层。

结果显示,转录组测序(RNA-Seq)与全基因组和外显子组测序的比较显示,独立的RNA-Seq测定提供了最大的诊断回报,能够识别表达的基因融合、单核苷酸和短插入/缺失变体,以及全转录组表达信息。

实验概述和短核苷酸变体分析

来自154名AML患者的表达数据被用来开发一个新的AML预后评分,在三个独立队列的620名患者和一个前瞻性队列的42名患者中,该评分与患者的预后密切相关。当与分子风险指南相结合时,该风险评分可以将来自三个独立队列的22.1%至25.3%的AML患者重新归入正确的风险组。

在不良风险亚组中,研究人员确定了一个以整合素信号失调和RUNX1或TP53突变为特征的患者亚组。研究人员进一步表明,这些患者可能从PTK2编码的局灶性粘附激酶抑制剂的治疗中获益,这表明基于转录组的测试在骨髓性恶性肿瘤的治疗选择中具有额外的效用。

 

原始出处:

T. Roderick Docking et al. A clinical transcriptome approach to patient stratification and therapy selection in acute myeloid leukemia. Nature Communications (2021). 

 

 

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    2021-08-12 liye789132251
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    2021-09-25 liuli5079
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    2021-05-30 mjldent
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