Human hematopoiesis: aging and leukemogenic risk.
Human hematopoiesis: aging and leukemogenic risk.
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DOI：
10.1097/moh.0000000000000622
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发表时间：
2021-01
影响因子：
3.2
通讯作者：
Figueroa ME
中科院分区：
文献类型：
--
作者：
Adelman ER;Figueroa ME
近年来，我们对衰老对人类造血的影响的理解取得了显著进展，但这些发现的全部含义尚未完全理解。本文综述了这些发现，并讨论了它们与恶性造血有关的意义。随着人类年龄的增长，免疫反应受损，HSC功能丧失，克隆造血增加，骨髓恶性肿瘤的频率更高。虽然小鼠模型涉及DNA损伤修复，自噬，代谢和表观遗传学的异常，但对原始人类标本的研究更为有限。年龄相关性克隆造血的发展及其相关风险是近年来该领域的主要发现之一。这伴随着骨髓干细胞和祖细胞组成的变化，干细胞表观遗传程序的变化和骨髓炎症环境的变化。这些变化对年龄相关恶性肿瘤发展的确切影响尚不清楚。该领域的进展已经开始揭示驱动人类HSC随年龄丧失功能的机制。为了更好地预防与年龄相关的髓系恶性肿瘤，区分正常和恶性衰老将是至关重要的。
Our understanding of the effects of aging on human hematopoiesis has advanced significantly in recent years, yet the full implications of these findings are not yet fully understood. This review summarizes these findings and discusses their implication as they relate to malignant hematopoiesis. With human aging there is an impaired immune response, loss of HSC function, increase in clonal hematopoiesis and higher frequency of myeloid malignancies. While murine models have implicated abnormalities in DNA damage repair, autophagy, metabolism and epigenetics, studies in primary human specimens are more limited. The development of age-related clonal hematopoiesis and the risk associated with this is one of the major findings in the field of recent years. This is accompanied by changes in bone marrow stem and progenitor composition, changes in the epigenetic program of stem cells and an inflammatory milieu in the bone marrow. The precise consequences of these changes for the development of age-related malignancies are still unclear. Advances in the field have begun to reveal the mechanisms driving human HSC loss of function with age. It will be critical to delineate between normal and malignant aging in order to better prevent age-associated myeloid malignancies.