Shlush Liran I, Zandi Sasan, Itzkovitz Shalev, Schuh Andre C
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network (UHN), 610 University Ave, Toronto, ON, M5G 2M9, Canada.
Weizmann Institute of Science, Rehovot, Israel.
Int J Hematol. 2015 Nov;102(5):513-22. doi: 10.1007/s12185-015-1870-5. Epub 2015 Oct 6.
Chronological human aging is associated with a number of changes in the hematopoietic system, occurring at many levels from stem to mature cells, and the marrow microenvironment as well. This review will focus mainly on the aging of hematopoietic stem and progenitor cells (HSPCs), and on the associated increases in the incidence of hematological malignancies. HSPCs manifest reduced function and acquire molecular changes with chronological aging. Furthermore, while for many years it has been known that the human hematopoietic system becomes increasingly clonal with chronological aging (clonal hematopoiesis), only in the last few years has it become clear that clonal hematopoiesis may result from the accumulation of preleukemic mutations in HSPCs. Such mutations confer a selective advantage that leads to clonal hematopoiesis, and that may occasionally result in the development of leukemia, and define the existence of both preleukemic stem cells, and of 'preleukemia' as a clinical entity. While it is well appreciated that clonal hematopoiesis is very common in the elderly, several questions remain unanswered: why and how does clonal hematopoiesis develop? How is clonal hematopoiesis related to the age-related changes observed in the hematopoietic system? And why do only some individuals with clonal hematopoiesis develop leukemia?
人类的生理性衰老与造血系统的一系列变化相关，这些变化发生在从干细胞到成熟细胞的多个层面，以及骨髓微环境中。本综述将主要关注造血干细胞和祖细胞（HSPCs）的衰老，以及血液系统恶性肿瘤发病率的相应增加。随着生理性衰老，HSPCs表现出功能减退并发生分子变化。此外，多年来人们已经知道，随着生理性衰老，人类造血系统会越来越多地出现克隆性（克隆造血），但直到最近几年才清楚地认识到，克隆造血可能是HSPCs中白血病前期突变积累的结果。这些突变赋予了一种选择性优势，导致克隆造血，偶尔可能导致白血病的发生，并确定了白血病前期干细胞以及作为一种临床实体的“白血病前期”的存在。虽然人们充分认识到克隆造血在老年人中非常普遍，但仍有几个问题没有答案：克隆造血为什么会发生以及如何发生？克隆造血与造血系统中观察到的与年龄相关的变化有何关系？为什么只有一些克隆造血的个体发展为白血病？
