Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Medical Oncology, Howard Hughes Medical Institute, Boston, MA.
Science. 2019 Nov 1;366(6465). doi: 10.1126/science.aan4673.
As people age, their tissues accumulate an increasing number of somatic mutations. Although most of these mutations are of little or no functional consequence, a mutation may arise that confers a fitness advantage on a cell. When this process happens in the hematopoietic system, a substantial proportion of circulating blood cells may derive from a single mutated stem cell. This outgrowth, called "clonal hematopoiesis," is highly prevalent in the elderly population. Here we discuss recent advances in our knowledge of clonal hematopoiesis, its relationship to malignancies, its link to nonmalignant diseases of aging, and its potential impact on immune function. Clonal hematopoiesis provides a glimpse into the process of mutation and selection that likely occurs in all somatic tissues.
随着年龄的增长,人体组织会积累越来越多的体细胞突变。尽管这些突变大多数没有什么功能影响,但是可能会出现一种赋予细胞生存优势的突变。当这个过程发生在造血系统时,相当一部分循环血细胞可能来源于单个突变的干细胞。这种生长被称为“克隆性造血”,在老年人群中非常普遍。在这里,我们讨论了近年来我们对克隆性造血的认识进展,包括它与恶性肿瘤的关系,与衰老相关非恶性疾病的联系,以及对免疫功能的潜在影响。克隆性造血为我们提供了一个了解突变和选择过程的窗口,而这个过程可能发生在所有的体细胞组织中。