EBV-driven B-cell lymphoproliferative disorders: from biology, classification and differential diagnosis to clinical management

  • Exp Mol Med. 2015 Jan 23;47(1):e132. doi: 10.1038/emm.2014.82.
Chi Young Ok  1 ,  Ling Li  2 ,  Ken H Young  3
Affiliations
  • 1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 2. 1] Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Medical Oncology, University of Zhengzhou School of Medicine, Zhengzhou, China.
  • 3. 1] Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX, USA.
PMID: 25613729 DOI: 10.1038/emm.2014.82
Abstract

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.