Distinct cellular origins of primary effusion lymphoma with and without EBV infection

Rifat Hamoudi, Tim C. Diss, Eric Oksenhendler, Langxing Pan, Antonino Carbone, Valeria Ascoli, Chris Boshoff, Peter Isaacson, Ming Qing Du

Research output: Contribution to journalArticle

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with three distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD) and germinotropic lymphoproliferative disorder (GLD). KSHV positive lymphocytes in GLD and in most cases of PEL are co-infected by Epstein-Barr virus (EBV) and these viral double positive cells harbour mutated rearranged immunoglobulin (Ig) genes, suggesting that they originate from germinal centre or post-germinal centre B-cells. In contrast, KSHV positive cells in MCD are invariably negative for EBV, do not carry Ig gene mutation and are believed to originate from naïve IgMλ expressing B-cells. Interestingly, one EBV negative PEL (BC3) also lacks Ig gene mutation, raising the question whether KSHV preferentially targets naïve B-cells in the absence of EBV. We compared the cellular origin of PEL with and without EBV infection by analysis of Ig gene mutation. High molecular weight DNA from 17 PELs was subjected to PCR of the rearranged Ig heavy and light chain genes. Successful amplification was achieved from eight cases (four EBV positive and four EBV negative) and the PCR products were sequenced. All four EBV positive PEL showed variable levels of mutation in their rearranged VH or VL genes, ranging from 4 to 7%. In contrast, two of the four EBV negative PELs including BC3 displayed absence of mutation in their rearranged Ig genes. Our results indicate that EBV positive PELs are derived from germinal centre or post-germinal centre B-cells, whereas EBV negative PELs may originate from either germinal/post-germinal centre or naïve B-cells.

Original languageEnglish
Pages (from-to)333-338
Number of pages6
JournalLeukemia Research
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 2004

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Keywords

  • EBV
  • Ig gene
  • Mutation
  • Primary effusion lymphoma

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Hamoudi, R., Diss, T. C., Oksenhendler, E., Pan, L., Carbone, A., Ascoli, V., Boshoff, C., Isaacson, P., & Du, M. Q. (2004). Distinct cellular origins of primary effusion lymphoma with and without EBV infection. Leukemia Research, 28(4), 333-338. https://doi.org/10.1016/j.leukres.2003.08.003