Abstract：
The age-related expansion of hematopoietic stem cell clones carrying somatic mutations is known as clonal hematopoiesis and is linked to hematologic malignancies, cardiovascular diseases, and increased mortality. As the risk for adverse outcomes increases substantially with clone size, a precise understanding of the mechanisms that promote clonal expansion is crucial to identify potential therapeutic targets. Clonal expansion and progression to myeloid malignancies are driven by a complex interplay of cell-intrinsic and extrinsic factors that remain incompletely understood. Here, we review how recently proposed methods to estimate clonal expansion rates have been implemented to study the natural history of clonal hematopoiesis and identify factors that promote clonal expansion. We discuss how these factors relate to progression to myeloid malignancies and recapitulate recent risk prediction models. While we are still in the early stages of understanding clonal expansion, analysis of large-scale biobank data in combination with experimental models will help to discover causal factors promoting or suppressing clone growth, define mechanisms, and identify potential targets for clinical intervention in the future.
摘要：
携带体细胞突变的造血干细胞克隆的与年龄相关的扩增被称为克隆造血，并与血液恶性肿瘤有关，心血管疾病,和死亡率增加。随着克隆大小的增加，不良后果的风险大大增加，准确了解促进克隆扩增的机制对于确定潜在的治疗靶点至关重要.克隆扩增和进展为髓样恶性肿瘤是由细胞内在和外在因素的复杂相互作用驱动的，这些因素仍未完全理解。这里,我们回顾了最近提出的估计克隆扩增率的方法是如何实施的，以研究克隆造血的自然史并确定促进克隆扩增的因素。我们讨论了这些因素如何与骨髓性恶性肿瘤的进展有关，并概述了最近的风险预测模型。虽然我们仍处于了解克隆扩张的早期阶段，结合实验模型分析大规模生物库数据将有助于发现促进或抑制克隆生长的因果因素，定义机制，并确定未来临床干预的潜在目标。
