Moores Cancer Center, University of California San Diego, La Jolla, CA.
Moores Cancer Center, University of California San Diego, La Jolla, CA.
Exp Hematol. 2020 Mar;83:105-112. doi: 10.1016/j.exphem.2020.02.001. Epub 2020 Feb 7.
Clonal hematopoiesis is a common premalignant condition defined by the abnormal expansion of clonally derived hematopoietic stem cells carrying somatic mutations in leukemia-associated genes. Apart from increasing age, this phenomenon occurs with higher frequency in individuals with lymphoid or solid tumors and is associated with exposures to genotoxic stress. Clonal hematopoiesis in this context confers a greater risk for developing therapy-related myeloid neoplasms and appears to contribute to adverse cancer-related survival through a variety of potential mechanisms. These include alterations of the bone marrow microenvironment, inflammatory changes in clonal effector cells and modulation of immune responses. Understanding how clonal hematopoiesis drives therapy-related myeloid neoplasm initiation and interactions with non-myeloid malignancies will inform screening and surveillance approaches and suggest targeted therapies in this vulnerable population. Here, we examine the clinical implications of clonal hematopoiesis in the cancer setting and discuss potential strategies to mitigate the adverse consequences of clonal expansion.
克隆性造血是一种常见的癌前状态,其特征为携带与白血病相关基因的体细胞突变的克隆性造血干细胞异常扩增。除了年龄增长之外,这种现象在患有淋巴或实体肿瘤的个体中更频繁发生,并且与遗传毒性应激的暴露相关。在这种情况下,克隆性造血会增加发展为治疗相关性髓系肿瘤的风险,并且似乎通过多种潜在机制导致癌症相关不良生存。这些机制包括骨髓微环境的改变、克隆效应细胞中的炎症变化以及免疫反应的调节。了解克隆性造血如何驱动治疗相关性髓系肿瘤的发生,以及与非髓系恶性肿瘤的相互作用,将为这一脆弱人群提供筛查和监测方法,并提示靶向治疗策略。在这里,我们研究了克隆性造血在癌症环境中的临床意义,并讨论了减轻克隆性扩增的不良后果的潜在策略。