Chan Irenaeus C C, Wiley Brian J, Bolton Kelly L
Washington University School of Medicine, St. Louis, MO, United States.
Front Oncol. 2022 Feb 8;12:794021. doi: 10.3389/fonc.2022.794021. eCollection 2022.
Clonal hematopoiesis (CH), defined as the clonal expansion of mutated hematopoietic stem and progenitor cells (HSPCs), is a common aging process. CH is a risk factor for the development of hematologic malignancies, most commonly myeloid neoplasms (MNs) including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN). Recent work has elucidated how the development and cellular fitness of CH is shaped by aging, environmental exposures, and the germline (inherited) genetic background of an individual. This in turn has provided valuable insights into the pathogenesis of MNs including MDS. Here, in this review, we discuss the genetic origins of CH, the environmental stressors that influence CH, and the implications of CH on health outcomes including MDS. Since MNs have shared risk factors and underlying biology, most of our discussion regarding the implications of CH surrounds MN in general rather than focusing specifically on MDS. We conclude with future directions and areas of investigation including how intervention studies of CH might inform future therapeutic approaches to MN including MDS.
克隆性造血（CH）被定义为突变的造血干细胞和祖细胞（HSPCs）的克隆性扩增，是一种常见的衰老过程。CH是血液系统恶性肿瘤发生的危险因素，最常见的是髓系肿瘤（MNs），包括急性髓系白血病（AML）、骨髓增生异常综合征（MDS）和骨髓增殖性肿瘤（MPN）。最近的研究阐明了衰老、环境暴露和个体的种系（遗传）基因背景如何塑造CH的发生发展和细胞适应性。这反过来又为包括MDS在内的MNs的发病机制提供了有价值的见解。在此综述中，我们讨论了CH的遗传起源、影响CH的环境应激源，以及CH对包括MDS在内的健康结局的影响。由于MNs有共同的危险因素和潜在生物学特性，我们关于CH影响的大部分讨论总体上围绕MNs，而不是特别关注MDS。我们最后展望了未来的方向和研究领域，包括CH的干预研究如何为包括MDS在内的MNs的未来治疗方法提供信息。
