Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Molecular Biology and Biochemistry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Stem Cell Reports. 2020 Aug 11;15(2):292-306. doi: 10.1016/j.stemcr.2020.06.021. Epub 2020 Jul 30.
Characterized by the expansion of somatic mutations in the hematopoietic lineages of aging individuals, clonal hematopoiesis of indeterminate potential (CHIP) is a common condition that increases the risk of developing hematological malignancies and cardiovascular disease (CVD). The presence of CHIP-associated mutations in hematopoietic stem and progenitor cells (HSPCs) suggests that these mutations may alter the functions of the diverse hematopoietic lineages, many of which influence the pathogenesis of CVD. Inflammation may be a potential pathogenic mechanism, linking both CVD and hematological malignancy. However, it remains unknown whether CHIP-associated CVD and hematological malignancy are features of a common disease spectrum. The contributions of CHIP-associated mutations to both CVD and hematological malignancy underscore the importance of stem cell biology in pathogenesis and treatment. This review discusses possible mechanisms underlying the contributions of multiple hematopoietic lineages to CHIP-associated CVD and the putative pathogenic links between CHIP-associated CVD and hematological malignancy.
特征为衰老个体造血谱系中体细胞突变的扩张,不确定潜能的克隆性造血(CHIP)是一种常见的病症,增加了发展为血液恶性肿瘤和心血管疾病(CVD)的风险。在造血干细胞和祖细胞(HSPC)中存在与 CHIP 相关的突变表明,这些突变可能改变不同造血谱系的功能,其中许多影响 CVD 的发病机制。炎症可能是一种潜在的发病机制,将 CVD 和血液恶性肿瘤联系在一起。然而,尚不清楚 CHIP 相关的 CVD 和血液恶性肿瘤是否是常见疾病谱的特征。CHIP 相关突变对 CVD 和血液恶性肿瘤的贡献强调了干细胞生物学在发病机制和治疗中的重要性。这篇综述讨论了多个造血谱系对 CHIP 相关 CVD 的贡献的可能机制,以及 CHIP 相关 CVD 和血液恶性肿瘤之间的潜在致病联系。