Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Lymphoma

Expression pattern of intracellular leukocyte-associated proteins in primary mediastinal B cell lymphoma

Leukemia volume 19, pages 856–861 (2005)Cite this article

Abstract

Two microarray studies of mediastinal B cell lymphoma have shown that this disease has a distinct gene expression profile, and also that this is closest to the pattern seen in classical Hodgkin's disease. We reported previously an immunohistologic study in which the loss of intracellular B cell-associated signaling molecules in Reed–Sternberg cells was demonstrated, and in this study we have investigated the expression of the same components in more than 60 mediastinal B cell lymphomas. We report that these signaling molecules are frequently present, and in particular that Syk, BLNK and PLC-γ2 (absent from Reed–Sternberg cells) are present in the majority of mediastinal B cell lymphomas. The overall pattern of B cell signaling molecules in this disease is therefore closer to that of diffuse large B cell lymphoma than to Hodgkin's disease, and is consistent with a common cell of origin as an explanation of the similar gene expression profiles.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Guiter C, Dusanter-Fourt I, Copie-Bergman C, Boulland ML, Le Gouvello S, Gaulard P et al. Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma. Blood 2004; 104: 543–549.

    Article  CAS  Google Scholar 

  2. Joos S, Otano-Joos MI, Ziegler S, Bruderlein S, du Manoir S, Bentz M et al. Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene. Blood 1996; 87: 1571–1578.

    CAS  PubMed  Google Scholar 

  3. Bentz M, Barth TF, Bruderlein S, Bock D, Schwerer MJ, Baudis M et al. Gain of chromosome arm 9p is characteristic of primary mediastinal B-cell lymphoma (MBL): comprehensive molecular cytogenetic analysis and presentation of a novel MBL cell line. Genes Chromosomes Cancer 2001; 30: 393–401.

    Article  CAS  Google Scholar 

  4. Joos S, Kupper M, Ohl S, von Bonin F, Mechtersheimer G, Bentz M et al. Genomic imbalances including amplification of the tyrosine kinase gene JAK2 in CD30+ Hodgkin cells. Cancer Res 2000; 60: 549–552.

    CAS  PubMed  Google Scholar 

  5. Joos S, Menz CK, Wrobel G, Siebert R, Gesk S, Ohl S et al. Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2. Blood 2002; 99: 1381–1387.

    Article  CAS  Google Scholar 

  6. Savage KJ, Monti S, Kutok JL, Cattoretti G, Neuberg D, De Leval L et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 2003; 102: 3871–3879.

    Article  CAS  Google Scholar 

  7. Rosenwald A, Wright G, Leroy K, Yu X, Gaulard P, Gascoyne RD et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003; 198: 851–862.

    Article  CAS  Google Scholar 

  8. Marafioti T, Pozzobon M, Hansmann ML, Delsol G, Pileri SA, Mason DY . Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin disease. Blood 2004; 103: 188–193.

    Article  CAS  Google Scholar 

  9. Jaffe SE, Harris LN, Stein H, Wardiman WJ . Mediastinal (thymic) large B-cell lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds). WHO Classification: Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon (France), 2001, pp 175–176.

    Google Scholar 

  10. Marafioti T, Jones M, Facchetti F, Diss TC, Du MQ, Isaacson PG et al. Phenotype and genotype of interfollicular large B cells, a subpopulation of lymphocytes often with dendritic morphology. Blood 2003; 102: 2868–2876.

    Article  CAS  Google Scholar 

  11. Mason DY, Micklem K, Jones M . Double immunofluorescence labelling of routinely processed paraffin sections. J Pathol 2000; 191: 452–461.

    Article  CAS  Google Scholar 

  12. Pozzobon M, Marafioti T, Hansmann ML, Natkunam Y, Mason DY . Intracellular signalling molecules as immunohistochemical markers of normal and neoplastic human leucocytes in routine biopsy samples. Br J Haematol 2004; 124: 519–533.

    Article  CAS  Google Scholar 

  13. Marafioti T, Pozzobon M, Hansmann M-L, Ventura R, Pileri SA, Roberton H et al. The NFATc1 transcription factor is widely expressed in white cells and translocates from the cytoplasm to the nucleus in a subset of human lymphomas. Br J Haem 2004; 128: 333–342.

    Article  Google Scholar 

  14. Pulford K, Falini B, Cordell J, Rosenwald A, Ott G, Muller-Hermelink HK et al. Biochemical detection of novel anaplastic lymphoma kinase proteins in tissue sections of anaplastic large cell lymphoma. Am J Pathol 1999; 154: 1657–1663.

    Article  CAS  Google Scholar 

  15. Cazals-Hatem D, Lepage E, Brice P, Ferrant A, d'Agay MF, Baumelou E et al. Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA (‘Groupe d'Etude des Lymphomes de l'Adulte’) study. Am J Surg Pathol 1996; 20: 877–888.

    Article  CAS  Google Scholar 

  16. Lazzarino M, Orlandi E, Paulli M, Strater J, Klersy C, Gianelli U et al. Treatment outcome and prognostic factors for primary mediastinal (thymic) B-cell lymphoma: a multicenter study of 106 patients. J Clin Oncol 1997; 15: 1646–1653.

    Article  CAS  Google Scholar 

  17. Barth TF, Dohner H, Werner CA, Stilgenbauer S, Schlotter M, Pawlita M et al. Characteristic pattern of chromosomal gains and losses in primary large B-cell lymphomas of the gastrointestinal tract. Blood 1998; 91: 4321–4330.

    CAS  PubMed  Google Scholar 

  18. Lamarre L, Jacobson JO, Aisenberg AC, Harris NL . Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases. Am J Surg Pathol 1989; 13: 730–739.

    Article  CAS  Google Scholar 

  19. Kanavaros P, Gaulard P, Charlotte F, Martin N, Ducos C, Lebezu M et al. Discordant expression of immunoglobulin and its associated molecule mb-1/CD79a is frequently found in mediastinal large B cell lymphomas. Am J Pathol 1995; 146: 735–741.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Barth TF, Leithauser F, Joos S, Bentz M, Moller P . Mediastinal (thymic) large B-cell lymphoma: where do we stand? Lancet Oncol 2002; 3: 229–234.

    Article  Google Scholar 

  21. Pileri SA, Gaidano G, Zinzani PL, Falini B, Gaulard P, Zucca E et al. Primary mediastinal B-cell lymphoma: high frequency of BCL-6 mutations and consistent expression of the transcription factors OCT-2, BOB.1, and PU.1 in the absence of immunoglobulins. Am J Pathol 2003; 162: 243–253.

    Article  CAS  Google Scholar 

  22. Tsang P, Cesarman E, Chadburn A, Liu YF, Knowles DM . Molecular characterization of primary mediastinal B cell lymphoma. Am J Pathol 1996; 148: 2017–2025.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Copie-Bergman C, Gaulard P, Maouche-Chretien L, Briere J, Haioun C, Alonso MA et al. The MAL gene is expressed in primary mediastinal large B-cell lymphoma. Blood 1999; 94: 3567–3575.

    CAS  PubMed  Google Scholar 

  24. Copie-Bergman C, Boulland ML, Dehoulle C, Moller P, Farcet JP, Dyer MJ et al. Interleukin 4-induced gene 1 is activated in primary mediastinal large B-cell lymphoma. Blood 2003; 101: 2756–2761.

    Article  CAS  Google Scholar 

  25. Copie-Bergman C, Plonquet A, Alonso MA, Boulland ML, Marquet J, Divine M et al. MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas. Mod Pathol 2002; 15: 1172–1180.

    Article  Google Scholar 

  26. Ruprai AK, Pringle JH, Angel CA, Kind CN, Lauder I . Localization of immunoglobulin light chain mRNA expression in Hodgkin's disease by in situ hybridization. J Pathol 1991; 164: 37–40.

    Article  CAS  Google Scholar 

  27. Lauritzen AF, Pluzek KJ, Kristensen LE, Nielsen HW . Detection of immunoglobulin light chain mRNA in nodular sclerosing Hodgkin's disease by in situ hybridization with biotinylated oligonucleotide probes compared with immunohistochemical staining with poly- and monoclonal antibodies. Histopathology 1992; 21: 353–358.

    Article  CAS  Google Scholar 

  28. Hell K, Pringle JH, Hansmann ML, Lorenzen J, Colloby P, Lauder I et al. Demonstration of light chain mRNA in Hodgkin's disease. J Pathol 1993; 171: 137–143.

    Article  CAS  Google Scholar 

  29. Marafioti T, Hummel M, Foss HD, Laumen H, Korbjuhn P, Anagnostopoulos I et al. Hodgkin and Reed–Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. Blood 2000; 95: 1443–1450.

    CAS  PubMed  Google Scholar 

  30. Schwering I, Brauninger A, Klein U, Jungnickel B, Tinguely M, Diehl V et al. Loss of the B-lineage-specific gene expression program in Hodgkin and Reed–Sternberg cells of Hodgkin lymphoma. Blood 2003; 101: 1505–1512.

    Article  CAS  Google Scholar 

  31. Addis BJ, Isaacson PG . Large cell lymphoma of the mediastinum: a B-cell tumour of probable thymic origin. Histopathology 1986; 10: 379–390.

    Article  CAS  Google Scholar 

  32. Isaacson PG, Norton AJ, Addis BJ . The human thymus contains a novel population of B lymphocytes. Lancet 1987; 2: 1488–1491.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Three grants supported this work: LRF (Ref Nos. 9970 and 0382) and the Julian Starmer-Smith Lymphoma Fund to DYM, Deutsche Krebshilfe to RS and Deutsche Krebshilfe (Ref No. 106367) to PM and TFB. We are grateful to Mr Ralf Lieberz and MS Roxanne Steinle for their help in preparing the tissue arrays, to Mrs Bridget Watson for her help in preparing the manuscript and to Dr Zheng Zhao for his invaluable advice concerning the presentation of the data.

Author information

Author notes

  1. P Möller and D Y Mason: These authors contributed equally to this work.

Authors and Affiliations

  1. Leukaemia Research Fund Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, UK

    T Marafioti, M Pozzobon, H Roberton, R Ventura & D Y Mason

  2. Senckenberg Pathology Institute, Johann Wolfgang Goethe-University Clinic Frankfurt am Main, Germany

    M-L Hansmann

  3. Department of Pathology, CHU Henri Mondor, University of Créteil, France

    P Gaulard & C Copie-Bergman

  4. Department of Pathology, University of Ulm, Germany

    T F Barth & P Möller

  5. Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel, Germany

    J I Martín-Subero & R Siebert

  6. Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada

    R D Gascoyne

  7. Department of Pathology and Unit of Haematopathology, Institute of Haematology ‘L&A Seragnoli’, University of Bologna, Italy

    S A Pileri

  8. Division of Pathology and Laboratory Medicine, Cleveland Clinic Foundation, OH, USA

    E D Hsi

  9. Department of Pathology, Stanford University School of Medicine, CA, USA

    Y Natkunam

Authors
  1. T Marafioti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Pozzobon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M-L Hansmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Gaulard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T F Barth
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Copie-Bergman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Roberton
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R Ventura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J I Martín-Subero
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. R D Gascoyne
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S A Pileri
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. R Siebert
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. E D Hsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Y Natkunam
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. P Möller
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. D Y Mason
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Marafioti.

Additional information

Supplementary Information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marafioti, T., Pozzobon, M., Hansmann, ML. et al. Expression pattern of intracellular leukocyte-associated proteins in primary mediastinal B cell lymphoma. Leukemia 19, 856–861 (2005). https://doi.org/10.1038/sj.leu.2403702

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403702

Keywords

This article is cited by

Search

Advanced search

Quick links