Liang Ying, Chen Xue, Zhang Xiuqun, Guo Caiping, Zhang Yulin
Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical University, Beijing, 100069, China.
Department of Hematology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Ann Hematol. 2024 Dec;103(12):4839-4849. doi: 10.1007/s00277-024-05959-7. Epub 2024 Aug 28.
In people living with HIV (PLWH), the susceptibility to malignancies is notably augmented, with lymphoma emerging as a predominant malignancy. Even in the antiretroviral therapy (ART) era, aggressive B-cell lymphoma stands out as a paramount concern. Yet, the pathogenesis of HIV related lymphoma (HRL) largely remains an enigma. Recent insights underscore the pivotal role of the dysregulated B cell receptor (BCR) signaling cascade, evidencing its oncogenic potential across a spectrum of lymphomas. Intricate interplays between HIV and BCR structural-functional integrity have been identified in PLWH. In this review, we elucidated the mechanism by which the BCR signaling pathway is involved in HRL, mainly including the following aspects: HIV can reshape BCR structure by modulating of activation-induced cytidine deaminase (AID) and recombination-activating gene (RAG) dynamics; HIV can act as a chronic antigen to activate the BCR signaling pathway, such as upregulating PI3K and MAPK signaling pathway and reducing the expression of CD300a; HIV co-infection with other oncogenic viruses may also influence tumor formation mediated by the BCR signaling pathway. This review aims to elucidate the intricate regulation of the BCR signaling pathway by HIV in B cell lymphoma, providing a novel perspective on the pathogenesis of lymphoma in HIV-affected environments.
在人类免疫缺陷病毒（HIV）感染者（PLWH）中，患恶性肿瘤的易感性显著增加，淋巴瘤成为主要的恶性肿瘤。即使在抗逆转录病毒治疗（ART）时代，侵袭性B细胞淋巴瘤仍是一个至关重要的问题。然而，HIV相关淋巴瘤（HRL）的发病机制在很大程度上仍然是个谜。最近的研究表明，失调的B细胞受体（BCR）信号级联起着关键作用，证明了其在一系列淋巴瘤中的致癌潜力。在PLWH中，已发现HIV与BCR结构-功能完整性之间存在复杂的相互作用。在本综述中，我们阐明了BCR信号通路参与HRL的机制，主要包括以下几个方面：HIV可通过调节活化诱导的胞苷脱氨酶（AID）和重组激活基因（RAG）的动力学来重塑BCR结构；HIV可作为慢性抗原激活BCR信号通路，如上调PI3K和MAPK信号通路并降低CD300a的表达；HIV与其他致癌病毒的共同感染也可能影响由BCR信号通路介导的肿瘤形成。本综述旨在阐明HIV在B细胞淋巴瘤中对BCR信号通路的复杂调节，为HIV感染环境中淋巴瘤的发病机制提供新的视角。
