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Blood, 1 November 2000, Vol. 96, No. 9, pp. 3133-3138

NEOPLASIA

Molecular single-cell analysis of the clonal relationship of small Epstein-Barr virus-infected cells and Epstein-Barr virus-harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease

Tilmann Spieker, Julia Kurth, Ralf Küppers, Klaus Rajewsky, Andreas Bräuninger, and Martin-Leo Hansmann

From the Department of Pathology, University of Frankfurt, Frankfurt, and the Institute for Genetics, University of Cologne, Cologne, Germany.

Epstein-Barr virus (EBV) can be detected in the tumor cells of approximately 40% of cases of classical Hodgkin disease (cHD). Clonality studies suggest that infection of the neoplastic Hodgkin and Reed/Sternberg (HRS) cells occurs before tumor clone expansion. In EBV-positive cases, variable numbers of EBER-positive small B cells are sometimes also observed that immunohistologically differ from the neoplastic cells by lack of CD30 and latent membrane protein 1 expression. To analyze the clonal relationship between these EBV+ cells and the HRS cells, single EBV-infected CD30- B cells, as well as HRS cells from 3 cases of EBV-positive cHD were micromanipulated, their immunoglobulin gene rearrangements amplified and then compared with each other. In 2 cases, all small EBV-infected cells were clonally unrelated to the HRS cells. In a third case, 2 of 29 small CD30- cells were found to carry HRS cell-specific rearrangements. Thus, small CD30- EBV-infected B cells in cHD belong to the HRS tumor clone rarely, if at all. In all cases, small clones unrelated to the HRS cell clones were identified among the small EBV+ CD30- cells. The vast majority of small EBV+ CD30- B cells was found to carry somatically mutated V region genes, indicating that in lymph nodes of patients with HD, like in the peripheral blood of healthy individuals, EBV persists in memory B cells.

© 2000 by The American Society of Hematology.
 

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