Abstract：
Clonal hematopoiesis in children and young adults differs from that occuring in the older adult population. A variety of stressors drive this phenomenon, sometimes independent of age-related processes. For the purposes of this review, we adopt the term clonal hematopoiesis in predisposed individuals (CHIPI) to differentiate it from classical, age-related clonal hematopoiesis of indeterminate potential (CHIP). Stress-induced CHIPI selection can be extrinsic, such as following immunologic, infectious, pharmacologic, or genotoxic exposures, or intrinsic, involving germline predisposition from inherited bone marrow failure syndromes. In these conditions, clonal advantage relates to adaptations allowing improved cell fitness despite intrinsic defects affecting proliferation and differentiation. In certain contexts, CHIPI can improve competitive fitness by compensating for germline defects; however, the downstream effects of clonal expansion are often unpredictable - they may either counteract the underlying pathology or worsen disease outcomes. A more complete understanding of how CHIPI arises in young people can lead to the definition of preleukemic states and strategies to assess risk, surveillance, and prevention to leukemic transformation. Our review summarizes current research on stress-induced clonal dynamics in individuals with germline predisposition syndromes.
摘要：
儿童和年轻人的克隆造血与老年人群的克隆造血不同。各种压力源驱动这种现象，有时与年龄相关的过程无关。就本次审查而言，我们采用易感个体中的克隆造血（CHIPI）这个术语来区分它与经典的，不确定潜力的年龄相关克隆造血（CHIP）。应激诱导的CHIPI选择可以是外在的，例如遵循免疫学，传染性,药理学,或基因毒性暴露，或者内在的，涉及遗传性骨髓衰竭综合征的种系倾向。在这些条件下,克隆优势与适应性有关，尽管固有缺陷会影响增殖和分化，但仍可以改善细胞适应性。在某些情况下，CHIPI可以通过补偿种系缺陷来提高竞争力；然而，克隆扩增的下游效应通常是不可预测的-它们可能抵消潜在的病理或恶化疾病结局.对CHIPI在年轻人中如何产生的更全面的了解可以导致白血病前期状态的定义和评估风险的策略，监视,和预防白血病转化。我们的综述总结了当前有关种系易感性综合征个体中应激诱导的克隆动力学的研究。
