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[克隆性造血对非血液系统疾病和衰老过程的影响]

[Influence of clonal hematopoiesis on non-hematological diseases and aging processes].

作者信息

Rieger Michael A

机构信息

Medizinische Klinik 2, Hämatologie/Onkologie, Klinikum der Goethe-Universität, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Deutschland.

Exzellenzcluster Cardio-Pulmonary Institute, Frankfurt am Main, Deutschland.

出版信息

Inn Med (Heidelb). 2022 Nov;63(11):1115-1125. doi: 10.1007/s00108-022-01409-6. Epub 2022 Oct 10.

DOI:10.1007/s00108-022-01409-6
PMID:36214849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9549812/
Abstract

The occurrence of clonal hematopoiesis, caused by acquired somatic mutations of leukemia-associated genes in blood stem cells is very common in the population and increases with age. Besides an increased risk of developing myeloid neoplasms, an unexpected causal relationship between clonal hematopoiesis and cardiovascular diseases was recently discovered. Clonal hematopoiesis presents as a new independent and strong risk factor for cardiovascular diseases, such as atherosclerosis, coronary heart disease, heart failure, aortic valve stenosis and stroke, which from a medical perspective should no longer be ignored. Worldwide intensive research for associations of clonal hematopoiesis with other age-related and infectious diseases identifies increasingly more illnesses that are influenced by the presence of mutated blood cells. Current data describe a fatal vicious circle, initiated by somatic blood cell mutations, which accelerate the progression of associated diseases in a proinflammatory way and feed-back to hematopoiesis leading to a further enlargement of the mutated blood cell clone. First experimental treatment approaches to break this vicious circle are discussed here. The causal relationship and the underlying pathomechanisms are now at the center of research interest in order to rapidly establish risk stratification and therapeutic measures for the benefit of patients in the near future.

摘要

由造血干细胞中白血病相关基因的获得性体细胞突变引起的克隆性造血在人群中非常普遍,且随年龄增长而增加。除了发生髓系肿瘤的风险增加外,最近还发现了克隆性造血与心血管疾病之间意想不到的因果关系。克隆性造血是心血管疾病(如动脉粥样硬化、冠心病、心力衰竭、主动脉瓣狭窄和中风)的一个新的独立且强大的危险因素,从医学角度来看,这一因素不应再被忽视。全球范围内对克隆性造血与其他年龄相关疾病和传染病关联的深入研究发现,越来越多的疾病受到突变血细胞存在的影响。目前的数据描述了一个由体细胞血细胞突变引发的致命恶性循环,这种突变以促炎方式加速相关疾病的进展,并反馈至造血过程,导致突变血细胞克隆进一步扩大。本文讨论了打破这一恶性循环的首批实验性治疗方法。因果关系及潜在的发病机制目前是研究的重点,以便在不久的将来迅速建立风险分层和治疗措施,造福患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/9549812/b7de06704dbc/108_2022_1409_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/9549812/82b1f8b86d71/108_2022_1409_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/9549812/591ceb108d4b/108_2022_1409_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/9549812/b7de06704dbc/108_2022_1409_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/9549812/82b1f8b86d71/108_2022_1409_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/9549812/591ceb108d4b/108_2022_1409_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/9549812/b7de06704dbc/108_2022_1409_Fig3_HTML.jpg

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本文引用的文献

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Association of Clonal Hematopoiesis of Indeterminate Potential with Inflammatory Gene Expression in Patients with COPD.克隆性造血不定潜能与 COPD 患者炎症基因表达的关联。
Cells. 2022 Jul 5;11(13):2121. doi: 10.3390/cells11132121.
2
TET2-Driven Clonal Hematopoiesis and Response to Canakinumab: An Exploratory Analysis of the CANTOS Randomized Clinical Trial.TET2 驱动的克隆性造血与卡那奴单抗反应:CANTOS 随机临床试验的探索性分析。
JAMA Cardiol. 2022 May 1;7(5):521-528. doi: 10.1001/jamacardio.2022.0386.
3
Increased prevalence of clonal hematopoiesis of indeterminate potential amongst people living with HIV.
HIV 感染者中克隆性造血的不确定潜能的患病率增加。
Sci Rep. 2022 Jan 12;12(1):577. doi: 10.1038/s41598-021-04308-2.
4
Association of clonal hematopoiesis with chronic obstructive pulmonary disease.克隆性造血与慢性阻塞性肺疾病的关联。
Blood. 2022 Jan 20;139(3):357-368. doi: 10.1182/blood.2021013531.
5
Clonal hematopoiesis is associated with risk of severe Covid-19.克隆性造血与严重 COVID-19 风险相关。
Nat Commun. 2021 Oct 13;12(1):5975. doi: 10.1038/s41467-021-26138-6.
6
The Cancer Therapy-Related Clonal Hematopoiesis Driver Gene Promotes Inflammation and Non-Ischemic Heart Failure in Mice.癌症治疗相关的克隆性造血驱动基因促进小鼠炎症和非缺血性心力衰竭
Circ Res. 2021 Sep 3;129(6):684-698. doi: 10.1161/CIRCRESAHA.121.319314. Epub 2021 Jul 28.
7
HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults.HIV 与老年人与年龄相关的克隆性造血增加有关。
Nat Med. 2021 Jun;27(6):1006-1011. doi: 10.1038/s41591-021-01357-y. Epub 2021 Jun 7.
8
Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction.克隆性造血与左心室射血分数降低的心力衰竭进展风险。
J Am Coll Cardiol. 2021 Apr 13;77(14):1747-1759. doi: 10.1016/j.jacc.2021.02.028.
9
Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality.慢性心力衰竭中克隆性造血驱动基因突变的全谱及其与死亡率的关联。
ESC Heart Fail. 2021 Jun;8(3):1873-1884. doi: 10.1002/ehf2.13297. Epub 2021 Mar 28.
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Nat Commun. 2021 Mar 23;12(1):1826. doi: 10.1038/s41467-021-22053-y.