髓系白血病
数字聚合酶链反应
突变
多路复用
酪氨酸激酶抑制剂
伊马替尼
癌症研究
达沙替尼
酪氨酸激酶
蛋白激酶结构域
肿瘤科
医学
生物
聚合酶链反应
内科学
遗传学
癌症
基因
突变体
信号转导
作者
Simona Soverini,Sara De Santis,Margherita Martelli,Cecilia Monaldi,Fausto Castagnetti,Gabriele Gugliotta,Cristina Papayannidis,Manuela Mancini,Samantha Bruno,Claudia Venturi,Kateřina Machová Poláková,Thomas Ernst,Dianna Maar,Adam S Corner,Michèle Cavo
出处
期刊:Leukemia
[Springer Nature]
日期:2022-07-30
卷期号:36 (9): 2250-2260
被引量:8
标识
DOI:10.1038/s41375-022-01660-8
摘要
One of the indications for BCR::ABL1 mutation testing in chronic myeloid leukemia (CML) is when tyrosine kinase inhibitor therapy (TKI) needs to be changed for unsatisfactory response. In this study, we evaluated a droplet digital PCR (ddPCR)-based multiplex strategy for the detection and quantitation of transcripts harbouring mutations conferring resistance to second-generation TKIs (2GTKIs). Parallel quantitation of e13a2, e14a2 and e1a2 BCR::ABL1 fusion transcripts enables to express results as percentage of mutation positive- over total BCR::ABL1 transcripts. We determined the limit of blank in 60 mutation-negative samples. Accuracy was demonstrated by further analysis of 48 samples already studied by next generation sequencing (NGS). Mutations could be called down to 0.5% and across 3-logs of BCR::ABL1 levels. Retrospective review of BCR::ABL1 NGS results in 513 consecutive CML patients with non-optimal response to first- or second-line TKI therapy suggested that a ddPCR-based approach targeted against 2GTKI-resistant mutations would score samples as mutation-negative in 22% of patients with warning response to imatinib but only in 6% of patients with warning response to 2GTKIs. We conclude ddPCR represents an attractive method for easy, accurate and rapid screening for 2GTKI-resistant mutations impacting on TKI selection, although ddPCR cannot identify compound mutations.
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