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在TKI治疗的白血病患者中,针对复杂的BCR-ABL1激酶域突变进行创新的快速查

Yanping Lan¹, Jun Deng², Pujing He¹

¹Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.

British journal of cancer

|June 30, 2025

概括

一个新的MeltArray-droplet数字PCR (ddPCR) 协议准确地描述了BCR-ABL1激酶域突变及其克隆关系. 这种方法有助于预测药物敏感性,并改善白血病患者的治疗结果.

科学领域:

血液学血液学血液学
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

查BCR-ABL1激酶域 (KD) 突变对于治疗慢性髓性白血病和费城阳性急性淋巴细胞白血病至关重要.
在治疗过程中,准确确定突变类型,丰度和克隆关系 (复合与多克隆突变) 是具有挑战性的.

研究的目的:

为选BCR-ABL1KD突变建立一个全面的协议.
要区分复合突变 (CMs) 和多克隆突变 (PMs).
为了实现对突变水平和克隆进化的动态监测,用于精确治疗.

主要方法:

结合MeltArray的迷你测序与滴滴数字PCR (ddPCR) 的等位基因分离.
开发了一种包括预放大,突变查和CM/PM差异化的协议.
对来自365名白血病患者的539个样本进行了回顾性分析.

主要成果:

在18.93%的样本中发现突变,其中35.9%的样本含有多个突变.
该协议区分PM (85.71%),CM (10.71%) 和混合型 (3.57%).
结果显示与下一代测序 (NGS) 具有很高的一致性,但存在较小的差异.

结论:

集成的MeltArray-ddPCR协议使得BCR-ABL1 KD突变和克隆状态的动态分析成为可能.
这种方法改善了对药物敏感性和白血病患者结果的预测.
提供伴随诊断以指导基于突变概况的精密治疗.

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