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向性病变和蛋白质体通过儿童急性淋巴细胞白血病的疾病演变预测治疗敏感性

Amanda C Lorentzian^1,2, Jenna Rever^1,2, Enes K Ergin^2,3

¹Department of Pediatrics, University of British Columbia, Vancouver, Canada.

Nature communications

|November 21, 2023

概括

儿童急性淋巴细胞白血病 (ALL) 复发源于正在发展的癌细胞. 蛋白质组分析显示PARP1是关键目标,显示ALL对PARP1/2抑制剂的敏感性,支持诊断时的精确瘤学.

科学领域:

在瘤学瘤学.
基因组学就是基因组学.
蛋白质组学是指蛋白质组学.

背景情况:

儿童急性淋巴细胞白血病 (ALL) 复发通常源于亚克隆基因扩张.
克隆进化对ALL可操作蛋白质组和向治疗反应的影响在很大程度上是未知的.

研究的目的:

为了研究克隆进化的影响可操作的蛋白质组在配对诊断和复发的童年ALL标本.
评估基因组变异,蛋白质组稳定性和针对性治疗的反应之间的相关性.

主要方法:

配对ALL诊断和复发样本的回顾性分析.
目标下一代测序和蛋白质组分析.
在体外药物敏感性测定使用可活冷活检.

主要成果:

可操作的基因组变异和蛋白质组从诊断到复发基本保持稳定.
实验室药物反应与变异向疗法相关,但选择性较低.
蛋白质组分析发现PARP1是关键的泛ALL目标,对细胞应激下生存至关重要.

结论:

在ALL中,PARP1是一个有前途的治疗标,诊断和复发样本都对PARP1/2抑制剂表现出敏感性.
未来的精确瘤学方法,包括在ALL诊断时进行蛋白质组分析,是有必要的.
蛋白质组分析可以预测瘤敏感性,可能在复发时持续存在.

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