Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells

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Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells

H Kanzler, R Kuppers, ML Hansmann and K Rajewsky
Institute for Genetics, University of Cologne, Germany.

In Hodgkin's disease (HD), the Hodgkin and Reed-Sternberg (HRS) cells represent only a minute population in the diseased tissue. The investigation of lineage derivation and clonal origin of these cells has yielded conflicting results. We have analyzed HRS cells micromanipulated from infiltrated tissue sections of 10 primary HD patients for rearranged V genes, extending a previous study. Clonally related rearrangements were found in nine cases, indicating that HRS cells represent a dominant clone of B lineage-derived cells in at least a large fraction of cases of HD. Rearranged VH genes from HRS cells carried a high load of somatic mutation, indicating that HRS cells are derived from germinal center (GC) cells or their progeny. Stop codons in some in-frame V gene rearrangements suggest that the HRS cell precursors reside inside GCs, have acquired crippling mutations that prevent antigenic selection, but escape apoptosis through some transforming event.
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Gravel, S., Delsol, G., Al Saati, T. (1998). Single-Cell Analysis of the t(14;18)(q32;q21) Chromosomal Translocation in Hodgkin's Disease Demonstrates the Absence of This Translocation in Neoplastic Hodgkin and Reed-Sternberg Cells. Blood 91: 2866-2874 [Abstract] [Full Text]
Messineo, C., Jamerson, M. H., Hunter, E., Braziel, R., Bagg, A., Irving, S. G., Cossman, J. (1998). Gene Expression by Single Reed-Sternberg Cells: Pathways of Apoptosis and Activation. Blood 91: 2443-2451 [Abstract] [Full Text]
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Ohno, T., Smir, B. N., Weisenburger, D. D., Gascoyne, R. D., Hinrichs, S. D., Chan, W. C. (1998). Origin of the Hodgkin/Reed-Sternberg Cells in Chronic Lymphocytic Leukemia With "Hodgkin's Transformation". Blood 91: 1757-1761 [Abstract] [Full Text]
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