EBV-driven B-cell lymphoproliferative disorders: from biology, classification and differential diagnosis to clinical management.
EBV-driven B-cell lymphoproliferative disorders: from biology, classification and differential diagnosis to clinical management.
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DOI：
10.1038/emm.2014.82
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发表时间：
2015-01-23
影响因子：
12.8
通讯作者：
Young, Ken H.
中科院分区：
文献类型：
--
作者：
Ok, Chi Young;Li, Ling;Young, Ken H.
EB病毒（EBV）是一种普遍存在的疱疹病毒，影响>90%的成年人群。EBV靶向B淋巴细胞，并以环状附加体形式实现潜伏感染。基于潜在基因表达模式识别不同的潜在模式。潜伏膜蛋白-1（LMP-1）模拟CD 40，并且当自聚集时，通过激活核因子-κ B、Janus激酶/信号转导和转录激活因子、磷酸肌醇3-激酶/Akt（PI 3 K/Akt）和促分裂原活化蛋白激酶途径提供增殖信号以促进细胞增殖。LMP-1还通过增强细胞周期蛋白依赖性激酶2和视网膜母细胞瘤（Rb）蛋白的磷酸化以及通过抑制p16和p27来诱导BCL-2逃避凋亡并给出细胞周期进展的信号。LMP-2A阻断表面免疫球蛋白介导的裂解周期再活化。它还激活Ras/PI 3 K/Akt通路并诱导Bcl-xL表达以促进B细胞存活。最近的研究表明ebv-microRNA可以为细胞增殖、细胞周期进程和抗凋亡提供额外的信号。众所周知，EBV与各种类型的B淋巴细胞、T淋巴细胞、上皮细胞和间充质细胞肿瘤相关。B细胞淋巴增生性疾病包括从良性到恶性的广泛疾病。在这里，我们回顾了我们目前对EB病毒诱导的淋巴瘤增生的了解，并重点关注EB病毒相关B细胞淋巴增生性疾病的生物学、诊断和管理。
Epstein–Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult population. EBV targets B-lymphocytes and achieves latent infection in a circular episomal form. Different latency patterns are recognized based on latent gene expression pattern. Latent membrane protein-1 (LMP-1) mimics CD40 and, when self-aggregated, provides a proliferation signal via activating the nuclear factor-kappa B, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase pathways to promote cellular proliferation. LMP-1 also induces BCL-2 to escape from apoptosis and gives a signal for cell cycle progression by enhancing cyclin-dependent kinase 2 and phosphorylation of retinoblastoma (Rb) protein and by inhibiting p16 and p27. LMP-2A blocks the surface immunoglobulin-mediated lytic cycle reactivation. It also activates the Ras/PI3K/Akt pathway and induces Bcl-xL expression to promote B-cell survival. Recent studies have shown that ebv-microRNAs can provide extra signals for cellular proliferation, cell cycle progression and anti-apoptosis. EBV is well known for association with various types of B-lymphocyte, T-lymphocyte, epithelial cell and mesenchymal cell neoplasms. B-cell lymphoproliferative disorders encompass a broad spectrum of diseases, from benign to malignant. Here we review our current understanding of EBV-induced lymphomagenesis and focus on biology, diagnosis and management of EBV-associated B-cell lymphoproliferative disorders.
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