在健康人群中预测急性髓性白血病风险
Sagi Abelson1, Grace Collord2,3, Stanley W K Ng4
1Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.
Nature
|July 11, 2018
概括
研究人员使用深度测序开发了一个模型,以区分白血病前突变和良性年龄相关的克隆造血,从而在诊断前几年能够早期发现急性髓性白血病 (AML) 的风险.
科学领域:
- 血液学
- 癌症学
- 遗传学
背景情况:
- 急性髓性白血病 (AML) 的发病率和死亡率随着年龄的增长而增加,通常与骨髓衰竭有关.
- 这种新型的AML是由造血干细胞和前代细胞 (HSPC) 的体质突变引起的,但在健康的老年人中也会发生类似的突变 (与年龄相关的克隆造血症,ARCH).
- 区分白血病前的ARCH与良性ARCH对于早期AML风险评估至关重要.
研究的目的:
- 使用深度测序来区分高风险的白血病前突变和良性与年龄相关的克隆造血 (ARCH).
- 开发一种针对急性髓性白血病 (AML) 的预测模型.
- 在独立的队列和电子健康记录中验证预测模型.
主要方法:
- 从AML前病例和年龄/性别匹配的对照中深度测序周围血液细胞.
- 对突变负担,变异性等位基因频率和基因突变丰富性的分析.
- 使用遗传参数和电子健康记录开发和验证无AML生存率和AML风险的预测模型.
主要成果:
- 与对照组相比,前AML病例呈现出显著更多的突变和更高的变异性等位基因频率.
- 在AML前组中,特定的基因突变被丰富,表明更大的克隆扩张.
- 该模型准确预测了没有AML的生存率,并确定了AML风险较高的个体.
结论:
- 在恶性转变前几年,可以区分良性与年龄相关的克隆造血 (ARCH) 和白血病前的疾病.
- 这种歧视可能使急性髓性白血病 (AML) 风险较高的个体能够更早地检测,监测和潜在的干预.
- 这些发现为早期的AML风险分层提供了概念验证.
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