Department of Life Sciences, Imperial College London, London, UK.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA; Department of Genetics, Stanford University School of Medicine, Stanford, CA.
Exp Hematol. 2019 Sep;77:1-5. doi: 10.1016/j.exphem.2019.08.004. Epub 2019 Aug 28.
Adult hematological malignancies, such as acute myeloid leukemia, are thought to arise through the gradual acquisition of oncogenic mutations within long-lived hematopoietic stem cells (HSCs). Genomic analysis of peripheral blood DNA has recently identified leukemia-associated genetic mutations within otherwise healthy individuals, an observation that is strongly associated with age. These genetic mutations are often found at high frequency, suggesting dominance of a mutant HSC clone. Expansion of clones carrying other mutations not associated with leukemia or larger chromosomal deletions was also observed. This clinical observation has been termed clonal hematopoiesis, a condition associated with increased risk of both hematological malignancy and cardiovascular disease. Here, we discuss the identification of clonal hematopoiesis and its implications on human health, based on the May 2019 International Society for Experimental Hematology New Investigator Committee Webinar.
成人血液系统恶性肿瘤，如急性髓系白血病，被认为是通过在长寿造血干细胞（HSCs）中逐渐获得致癌突变而产生的。最近对外周血 DNA 的基因组分析在其他健康个体中发现了与白血病相关的遗传突变，这一观察结果与年龄密切相关。这些遗传突变通常以高频出现，提示突变的 HSC 克隆占主导地位。还观察到携带其他与白血病无关的突变或更大染色体缺失的克隆的扩增。这种临床观察被称为克隆性造血，它与血液系统恶性肿瘤和心血管疾病风险的增加有关。在这里，我们根据 2019 年 5 月国际实验血液学学会新研究员委员会网络研讨会，讨论了克隆性造血的鉴定及其对人类健康的影响。
