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An epidemiologist’s view of the new molecular biology findings in Hodgkin’s disease

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Annals of Oncology

Summary

Recent advances in molecular biology provide new strategies to address the pathogenesis of Hodgkin’s disease (HD). Immunophenotyping studies of Reed-Sternberg cells suggest lymphoid cells, ‘frozen in a state of activation.’ Clonal rearrangement studies find heavy and light chain immunoglobulin and β and Г T-cell receptor gene changes. Chromosomal studies find a complex but nonrandom mixture of structural rearrangements including many seen in other hematologic disorders. These findings are consistent with a pathogenesis involving chronic antigenic stimulation. This interpretation is supported by the epidemiologic features of HD which suggest that HD may develop as a rare consequence of infection with a common latent virus where risk is increased if infection is delayed until adolescence or young adulthood. Such ‘late ’ infections are generally more clinically severe and may result in more chronicity of virus replication. Serologic and genome probe studies of the Epstein-Barr virus — a candidate agent — in HD specimens support this hypothesis. In summary, the new molecular biology findings in HD converge with the previous epidemiologic, immunologic, and clinical data to support a unifying hypothesis of pathogenesis in which genetic abnormalities occur secondarily to a sustained host response to chronic tissue-based antigenic stimulation.

Dr. Mueller is a recipient of an American Cancer Society Faculty Research Award.

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References

  1. Drexler HG, Leber BE The nature of the Hodgkin cell. Report of the First International Symposium on Hodgkin’s Lymphoma, Kohl, FRG, October 2–3, 1987. Blut 1988; 56: 135–137.

    Article  PubMed  CAS  Google Scholar 

  2. Hsu S-M, Hsu P-L. Aberrant expression of T cell and B cell markers in myelocyte/monocyte/histiocyte-derived lymphoma and leukemia cells: Is the infrequent expression of T/B cell markers sufficient to establish a lymphoid origin for Hodgkin’s Reed-Sternberg cells? Am J Pathol 1989; 134: 203–212.

    PubMed  CAS  Google Scholar 

  3. Andreesen R, Brugger W, Lohn GW et al. Human macrophage can express the Hodgkin’s cell-associated antigen Ki-1 (CD30). Am J Pathol 1989; 134: 187–192.

    PubMed  CAS  Google Scholar 

  4. Griesser H, Mak TW. Immunogenotyping in Hodgkin’s disease. Hematol Oncol 1988; 6: 239–245.

    Article  PubMed  CAS  Google Scholar 

  5. Griesser H, Feller A, Lennert K et al. Rearrangement of the ß chain of the T cell antigen receptor and immunoglobulin genes in lymphoproliferative disease. J Clin Invest 1986; 78: 1179–1184.

    Article  PubMed  CAS  Google Scholar 

  6. Griesser H, Feller AC, Mak TW et al. Clonal rearrangements of T-cell receptor and immunoglobulin genes and immunophenotypic antigen expression in different subclasses of Hodgkin’s disease. Int J Cancer 1987; 40: 157–160.

    Article  PubMed  CAS  Google Scholar 

  7. Knowles II DM, Neri A, Pelicci PG et al Immunoglobulin and T-cell receptor 13-chain gene rearrangement analysis of Hodgkin’s disease: Implications for lineage determination and differential diagnosis. Proc Natl Acad Sci USA 1986; 83: 7942–7946.

    Article  PubMed  CAS  Google Scholar 

  8. Weiss LM, Strickler JG, Hu E et al. Immunoglobulin gene rearrangements in Hodgkin’s disease. Hum Pathol 1986; 17: 1009–1014.

    Article  PubMed  CAS  Google Scholar 

  9. Brinker MGL, Poppema S, Buys GHCM et al. Clonal immunoglobulin gene rearrangements in tissues involved by Hodgkin’s disease. Blood 1987; 70: 186–191.

    PubMed  CAS  Google Scholar 

  10. O’Connor NTJ, Crick JA, Gatterk C et al. Cell lineage in Hodgkin’s disease. Lancet 1987; is 158.

    Google Scholar 

  11. Sundeen J, Lipford E, Uppenkamp M et al. Rearranged antigen receptor genes in Hodgkin’s disease. Blood 1987; 70: 96–103.

    PubMed  CAS  Google Scholar 

  12. Raghavachar A, Binder T, Bartram CR Immunoglobulin and T cell receptor gene rearrangements in human leukaemias and lymphomas. Cancer Res 1988; 48: 3591–3594.

    PubMed  CAS  Google Scholar 

  13. Roth MS, Schnitzer B, Bingham EL et al. Rearrangement of immunoglobulin and T-cell receptor genes in Hodgkin’s disease. Am J Pathol 1988; 131: 331–338.

    PubMed  CAS  Google Scholar 

  14. Daus H, Schwarze G, Kumel G et al. Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin’s disease. Acta Haemat 1989; 82: 110–111.

    Article  PubMed  CAS  Google Scholar 

  15. Herbst H, Tippelmann G, Anagnostopoulos I et al. Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin’s disease and Ki-1-positive anaplastic large cell lymphoma: Dissociation between phenotype and genotype. Leuk Res 1989; 13: 103–116.

    Article  PubMed  CAS  Google Scholar 

  16. Drexler HG, Johns DB, Diehl V et al. Is the Hodgkin cell a Tor B-lymphocyte? Recent evidence from geno- and immunophenotypic analysis and in-vitro cell lines. Hematol Oncol 1989; 7: 95–113.

    Article  PubMed  CAS  Google Scholar 

  17. Cabanillas E A review and interpretation of cytogenetic abnormalities identified in Hodgkin’s disease. Hematol Oncol 1988; 271–274.

    Google Scholar 

  18. Hossfeld DK, Schmidt CG. Chromosome findings in effusions from patients with Hodgkin’s disease. Int J Cancer 1978; 21: 147–156.

    Article  PubMed  CAS  Google Scholar 

  19. Reeves BR, Pickup VL. The chromosome changes in non-Burkitt lymphomas. Hum Genet 1980; 53: 349–355.

    PubMed  CAS  Google Scholar 

  20. Fleishman T. Reported in Rowley JD. Chromosomes in Hodgkin’s disease. Cancer Treat Rep 1982; 66: 639–643.

    Google Scholar 

  21. Fonatsch C, Diehl V, Schaadt M et al. Cytogenetic investigations in Hodgkin’s disease. I. Involvement of specific chromosomes in marker formation. Cancer Genet Cytogenet 1986; 20: 39–52.

    Article  PubMed  CAS  Google Scholar 

  22. Cabanillas F, Pathak S, Trujillo J et al. Cytogenetics of Hodgkin’s disease suggest possible origin from a lymphocyte. Blood 1988; 71: 1615–1617.

    PubMed  CAS  Google Scholar 

  23. Thangavelu M, LeBeau MM. Chromosomal abnormalities in Hodgkin’s disease. Hemat/Oncol Clin N Amer 1989; 3: 22 1236.

    Google Scholar 

  24. Romagnani S, Ferrini PLS, Rici M. The immune derangement in Hodgkin’s disease. Sem Hematol 1985; 22: 41–55.

    CAS  Google Scholar 

  25. Ford RI, Tsao J, Kouttab NM et al. Association of an interleukin abnormality with the T cell defect in Hodgkin’s disease. Blood 1984; 64: 386–392.

    PubMed  CAS  Google Scholar 

  26. Ford RJ, Rajaraman C, Lu M et al. In vitro analysis of cell populations involved in Hodgkin’s disease lesions and in the characteristic T cell immunodeficiency. Hematol Oncol 1988; 6: 247–255.

    Article  PubMed  CAS  Google Scholar 

  27. Pizzolo G, Chilosi M, Vinante F et al. Soluble interleukin-2 receptors in the serum of patients with Hodgkin’s disease. Br J Cancer 1987; 55: 427–428.

    Article  PubMed  CAS  Google Scholar 

  28. Gutensohn (Mueller) N, Cole P. Childhood social environment and Hodgkin’s disease. N Engl J Med 1981; 304: 135–140.

    Article  PubMed  CAS  Google Scholar 

  29. MacMahon B. The epidemiologic evidence on the nature of Hodgkin’s disease. Cancer 1957; 10: 1045–1054.

    Article  PubMed  CAS  Google Scholar 

  30. MacMahon B. Epidemiology of Hodgkin’s disease. Cancer Res 1966; 26: 1189–1200.

    PubMed  CAS  Google Scholar 

  31. Correa P, O’Connor GT. Epidemiologic patterns of Hodgkin’s disease. Int J Cancer 1971; 8: 192–201.

    Article  PubMed  CAS  Google Scholar 

  32. Gutensohn (Mueller) N, Cole P. Epidemiology of Hodgkin’s disease in the young. Int J Cancer 1977; 19: 595–604.

    Article  PubMed  CAS  Google Scholar 

  33. Mueller N. Hodgkin’s disease. In D. Schottenfeld, J. Fraumeni, Jr. (eds). Cancer Epidemiology and Prevention, Second Edition, New York, Oxford University Press (in press).

    Google Scholar 

  34. Gutensohn (Mueller) N. Social class and age at diagnosis of Hodgkin’s disease: New epidemiology evidence on the ‘two-disease’ hypothesis. Cancer Treat Rep 1982; 66: 689–695.

    Google Scholar 

  35. Evans AS. The Epstein-Barr virus. In A. Evans (ed.) Viral infections in Humans: Epidemiology and Control, Third Edition, New York, Plenum Press (in press).

    Google Scholar 

  36. Evans AS, Gutensohn (Mueller) NM. A population-based case-control study of EBV and other viral antibodies among persons with Hodgkin’s disease and their siblings. Int J Cancer 1984; 34: 149–157.

    Article  PubMed  CAS  Google Scholar 

  37. Mueller N, Evans A, Harris NL et al. Hodgkin’s disease and Epstein-Barr virus: Altered antibody patterns before diagnosis. N Engl J Med 1989; 320: 689–695.

    Article  PubMed  CAS  Google Scholar 

  38. Weiss LM, Strickler JG, Warnke RA et al. Epstein-Barr viral DNA in tissues of Hodgkin’s disease. Am J Pathol 1987; 129: 86–91.

    PubMed  CAS  Google Scholar 

  39. Weiss LM, Movahed LA, Warnke RA et al. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin’s disease. N Engl J Med 1989; 320: 502–506.

    Article  PubMed  CAS  Google Scholar 

  40. Staal SP, Ambinder R, Beschorner WE et al. A survey of Epstein-Barr virus DNA in lymphoid tissue: Frequent detec-tion in Hodgkin’s disease. Am J Clin Path 1989; 91: 1–5.

    PubMed  CAS  Google Scholar 

  41. Anagnostopoulos I, Herbst H, Niedobitek G et al. Demonstration of monoclonal EBV genomes in Hodgkin’s disease and Ki-1 positive anaplastic large cell lymphoma by combined southern blot and in situ hybridization. Blood 1989; 74: 810816.

    Google Scholar 

  42. Uhara H, Sato Y, Mukai K et al. Detection of Epstein-Barr virus DNA in Reed-Sternberg cells of Hodgkin’s disease using the polymenase chain reaction and in situ hybridization. Jpn J Cancer Res 1990; 81: 272–278.

    Article  PubMed  CAS  Google Scholar 

  43. Smithers D. On some general concepts in oncology with spe cial references to Hodgkin’s disease. Int J Radiation Oncol Biol Phys 1983; 9: 731–738.

    Article  CAS  Google Scholar 

  44. Gutensohn (Mueller) NM. The epidemiology of Hodgkin’s disease: Clues to Etiology. In RJ Ford, LM Fuller and FB Hagemeister (eds.) Ut M.D. Anderson Clinical Conference on Cancer, Vol. 27, Raven Press, New York, 1984, pp 3–9.

    Google Scholar 

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Authors and Affiliations

  1. Harvard School of Public Health, Boston, Massachusetts, USA

    Nancy Mueller Sc.D.

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  1. Nancy Mueller Sc.D.
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Editors and Affiliations

  1. Section of Hematology/Oncology, Department of Medicine, The University of Chicago Cancer Research Center, Chicago, Illinois, USA

    John E. Ultmann  & Brian L. Samuels  & 

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© 1991 Springer Science+Business Media Dordrecht

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Mueller, N. (1991). An epidemiologist’s view of the new molecular biology findings in Hodgkin’s disease. In: Ultmann, J.E., Samuels, B.L. (eds) Annals of Oncology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7305-4_3

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  • DOI: https://doi.org/10.1007/978-1-4899-7305-4_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-7294-1

  • Online ISBN: 978-1-4899-7305-4

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