DOI: 10.1073/pnas.94.17.9337. Hodgkin and Reed–Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells

Hodgkin and Reed–Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells

10.1073/pnas.94.17.9337

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Among the four subtypes of Hodgkin disease (HD), lymphocyte-predominant (LP) HD is now generally considered as a separate entity. The B cell nature of the typical Hodgkin and Reed–Sternberg (HRS) cells and their variants (L and H, lymphocytic and histiocytic cells) in LP HD has long been suspected, but the question of whether these cells represent a true tumor clone is unclear. We previously demonstrated clonal Ig gene rearrangements in one case of LP HD. In the present study, five cases of LP HD were analyzed by micromanipulation of single HRS cells from frozen tissue sections and DNA amplification of rearranged Ig heavy chain genes from those cells. Clonal V gene rearrangements harboring somatic mutations were detected in each case. In three cases ongoing somatic mutation was evident. This shows that HRS cells in LP HD are a clonal tumor population derived from germinal center B cells. The pattern of somatic mutation indicates that HRS cells in LP HD are selected for antibody expression. This, and the presence of ongoing mutation discriminates LP from classical HD.

Bibliography

Braeuninger, A., KÃ¼ppers, R., Strickler, J. G., Wacker, H.-H., Rajewsky, K., & Hansmann, M.-L. (1997). Hodgkin and ReedâSternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor Bâcells. Proceedings of the National Academy of Sciences, 94(17), 9337â9342.

Authors 6

Andreas Braeuninger (first)
Ralf Küppers (additional)
John G. Strickler (additional)
Hans-Heinrich Wacker (additional)
Klaus Rajewsky (additional)
Martin-Leo Hansmann (additional)

References 41 Referenced 224

J S Burke Neoplastic Hematopathology, ed D M Knowles (Williams & Wilkins, Baltimore), pp. 497–533 (1992). / Neoplastic Hematopathology by Burke J S (1992)
10.1182/blood.V84.5.1361.1361
10.1097/00000478-199405000-00014
10.1002/j.1460-2075.1993.tb06189.x
10.1002/eji.1830231232
10.1084/jem.180.4.1383
10.1084/jem.180.1.329
10.1038/354389a0
10.1016/S0065-2776(08)60587-8
10.1016/S0065-2776(08)60426-5
10.1073/pnas.91.23.10962
10.1182/blood.V87.8.3429.bloodjournal8783429
10.1084/jem.184.4.1495
W Timens, L Visser, S Poppema Lab Invest 54, 457–461 (1986). / Lab Invest by Timens W (1986)
F B Coles, R W Cartun, W T Pastuszak Mod Pathol 1, 274–278 (1986). / Mod Pathol by Coles F B (1986)
10.1111/j.1365-2559.1993.tb00092.x
10.1111/j.1365-2559.1994.tb00568.x
10.1093/ajcp/86.3.292
10.1002/path.1711710211
M H Stoler, G E Nichols, M Symbula, L M Weiss Am J Pathol 146, 812–818 (1995). / Am J Pathol by Stoler M H (1995)
R van Wasielewski, L Wilkens, M Nolte, M Werner, A Georii Mod Pathol 9, 334–338 (1996). / Mod Pathol by van Wasielewski R (1996)
10.1007/BF00390466
10.1056/NEJM198801283180404
10.1182/blood.V87.6.2428.bloodjournal8762428
10.1182/blood.V84.10.3291.3291
Küppers R. Kanzler H. Hansmann M. L. & Rajewsky K. (1996) Ann. Oncol. 7 (Suppl. 4) S27–S30. (10.1093/annonc/7.suppl_4.S27)
10.1007/BF03401587
10.1002/eji.1830270616
10.1038/ng0193-88
10.1084/jem.173.2.395
10.1182/blood.V89.4.1288
10.1093/ajcp/95.2.194
10.1007/BF02128186
10.1182/blood.V87.2.465.bloodjournal872465
10.1016/0092-8674(86)90488-5
10.1073/pnas.89.15.6770
10.1111/j.1600-065X.1992.tb00636.x
10.1084/jem.173.1.197
10.1111/j.1365-2141.1994.tb04780.x
10.1111/j.1365-3083.1995.tb03625.x
10.1182/blood.V80.4.879.879

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:42 a.m.)
Deposited	3 years, 2 months ago (June 6, 2022, 5:25 p.m.)
Indexed	5 days, 19 hours ago (Aug. 28, 2025, 8:31 a.m.)
Issued	28 years ago (Aug. 19, 1997)
Published	28 years ago (Aug. 19, 1997)
Published Online	28 years ago (Aug. 19, 1997)
Published Print	28 years ago (Aug. 19, 1997)

Funders 0

None

BibTeX

@article{Braeuninger_1997, title={Hodgkin and Reed–Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.17.9337}, DOI={10.1073/pnas.94.17.9337}, number={17}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Braeuninger, Andreas and Küppers, Ralf and Strickler, John G. and Wacker, Hans-Heinrich and Rajewsky, Klaus and Hansmann, Martin-Leo}, year={1997}, month=aug, pages={9337–9342} }

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