Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle

Martina Vockerodt, Wenbin Wei, Eszter Nagy, Zuzana Prouzova, Alexandra Schrader, Dieter Kube, Martin Rowe, Ciaran Woodman, Paul Murray

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Hodgkin’s lymphoma is unusual among B cell lymphomas insofar as the malignant Hodgkin/Reed‐Sternberg (HRS) cells lack a functional B cell receptor (BCR) as well as many of the required downstream signalling components. In Epstein‐Barr virus (EBV)‐positive cases of Hodgkin’s lymphoma, HRS cells express the viral latent membrane proteins (LMP)‐1 and ‐2A. LMP2A is thought to contribute to the pathogenesis of Hodgkin’s lymphoma by providing a surrogate BCR‐like survival signal. However, LMP2A has also been shown to induce the virus replicative cycle in B cells, an event presumably incompatible with lymphomagenesis. In an attempt to resolve this apparent paradox we compared the transcriptional changes observed in primary HRS cells with those induced by LMP2A and by BCR activation in primary human germinal centre (GC) B cells, the presumed progenitors of HRS cells. We found a subset of genes that were up‐regulated by both LMP2A expression and BCR activation but which were down‐regulated in primary HRS cells. These genes included EGR1, an immediate‐early gene that is required for BCR‐induced entry to the virus replicative cycle. We present data supporting a model for the pathogenesis of EBV‐positive Hodgkin’s lymphoma in which LMP2A‐expressing HRS cells lacking BCR signalling functions cannot induce EGR1 and are consequently protected from entry to the virus lytic cycle.
Original languageEnglish
Pages (from-to)399-409
Number of pages11
JournalJournal of Pathology
Issue number4
Early online date16 Apr 2013
Publication statusPublished - Aug 2013

Bibliographical note

Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


  • Hodgkin lymphoma
  • EBV lytic cycle

ASJC Scopus subject areas

  • General Medicine


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