Somatic or acquired mutations are postzygotic genetic variations that can occur within any tissue. These mutations accumulate during aging and have classically been linked to malignant processes. Tremendous advancements over the past years have led to a deeper understanding of the role of somatic mutations in benign and malignant age-related diseases. Here, we review the somatic mutations that accumulate in the blood and their connection to disease states, with a particular focus on inflammatory diseases and myelodysplastic syndrome. We include a definition of clonal hematopoiesis (CH) and an overview of the origins and implications of these mutations. In addition, we emphasize somatic disorders with overlapping inflammation and hematologic disease beyond CH, including paroxysmal nocturnal hemoglobinuria and aplastic anemia, focusing on VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Finally, we provide a practical view of the implications of somatic mutations in clinical hematology, pathology, and beyond.

中文翻译：

---

克隆性造血、炎症和血液系统恶性肿瘤


体细胞或获得性突变是合子后遗传变异，可以发生在任何组织内。这些突变在衰老过程中积累，通常与恶性过程有关。过去几年的巨大进步使人们对体细胞突变在良性和恶性年龄相关疾病中的作用有了更深入的了解。在这里，我们回顾了血液中积累的体细胞突变及其与疾病状态的联系，特别关注炎症性疾病和骨髓增生异常综合征。我们包括克隆性造血 （CH） 的定义以及这些突变的起源和影响的概述。此外，我们强调重叠炎症的躯体疾病和 CH 以外的血液系统疾病，包括阵发性睡眠性血红蛋白尿症和再生障碍性贫血，重点关注 VEXAS （空泡、E1 酶、X 连锁、自身炎症、躯体）综合征。最后，我们提供了体细胞突变对临床血液学、病理学等影响的实用观点。