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人类免疫缺陷病毒与克隆性造血

Human Immunodeficiency Virus and Clonal Hematopoiesis.

机构信息

Division of Pediatric Oncology, Department of Oncology, Johns Hopkins University Hospital, Baltimore, MD 21287, USA.

Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.

出版信息

Cells. 2023 Feb 22;12(5):686. doi: 10.3390/cells12050686.

Abstract

The evolution of antiretroviral therapies (ART) has tremendously improved the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH), which is currently similar to the general population. However, as PLWH are now living longer, they exhibit various comorbidities such as a higher risk of cardiovascular disease (CVD) and non-acquired immunodeficiency syndrome (AIDS)-defined malignancies. Clonal hematopoiesis (CH) is the acquisition of somatic mutations by the hematopoietic stem cells, rendering them survival and growth benefit, thus leading to their clonal dominance in the bone marrow. Recent epidemiologic studies have highlighted that PLWH have a higher prevalence of CH, which in turn is associated with increased CVD risk. Thus, a link between HIV infection and a higher risk for CVD might be explained through the induction of inflammatory signaling in the monocytes carrying CH mutations. Among the PLWH, CH is associated with an overall poorer control of HIV infection; an association that requires further mechanistic evaluation. Finally, CH is linked to an increased risk of progression to myeloid neoplasms including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which are associated with particularly poor outcomes among patients with HIV infection. These bidirectional associations require further molecular-level understanding, highlighting the need for more preclinical and prospective clinical studies. This review summarizes the current literature on the association between CH and HIV infection.

摘要

抗逆转录病毒疗法 (ART) 的发展极大地提高了人类免疫缺陷病毒 (HIV) 感染者 (PLWH) 的预期寿命,目前与普通人群相似。然而,随着 PLWH 的寿命延长,他们表现出各种合并症,如心血管疾病 (CVD) 和非获得性免疫缺陷综合征 (AIDS) 定义的恶性肿瘤的风险更高。克隆性造血 (CH) 是造血干细胞获得体细胞突变,使它们具有生存和生长优势,从而导致它们在骨髓中克隆优势。最近的流行病学研究强调,PLWH 中 CH 的患病率更高,而 CH 反过来又与 CVD 风险增加相关。因此,HIV 感染与 CVD 风险增加之间的联系可能通过携带 CH 突变的单核细胞中炎症信号的诱导来解释。在 PLWH 中,CH 与 HIV 感染总体控制较差有关;这种关联需要进一步的机制评估。最后,CH 与骨髓增生性肿瘤(包括骨髓增生异常综合征 [MDS] 和急性髓系白血病 [AML])的进展风险增加相关,这些肿瘤与 HIV 感染患者的预后特别差有关。这些双向关联需要更深入的分子水平理解,突出了需要进行更多的临床前和前瞻性临床研究。这篇综述总结了目前关于 CH 与 HIV 感染之间关联的文献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8213/10001188/99c6123f782f/cells-12-00686-g001.jpg

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