Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma

Andreas Rosenwald, George Wright, Karen Leroy, Xin Yu, Philippe Gaulard, Randy D. Gascoyne, Wing C. Chan, Tong Zhao, Corinne Haioun, Timothy C. Greiner, Dennis D. Weisenburger, James C. Lynch, Julie Vose, James O. Armitage, Erlend B. Smeland, Stein Kvaloy, Harald Holte, Jan Delabie, Elias Campo, Emili MontserratArmando Lopez-Guillermo, German Ott, H. Konrad Muller-Hermelink, Joseph M. Connors, Rita Braziel, Thomas M. Grogan, Richard I. Fisher, Thomas P. Miller, Michael LeBlanc, Michael Chiorazzi, Hong Zhao, Liming Yang, John Powell, Wyndham H. Wilson, Elaine S. Jaffe, Richard Simon, Richard D. Klausner, Louis M. Staudt

Research output: Contribution to journalArticle

805 Scopus citations

Abstract

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.

Original languageEnglish (US)
Pages (from-to)851-862
Number of pages12
JournalJournal of Experimental Medicine
Volume198
Issue number6
DOIs
StatePublished - Sep 15 2003

Keywords

  • DLBCL
  • Gene expression profiling
  • Microarray
  • Outcome prediction
  • PMBL

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rosenwald, A., Wright, G., Leroy, K., Yu, X., Gaulard, P., Gascoyne, R. D., Chan, W. C., Zhao, T., Haioun, C., Greiner, T. C., Weisenburger, D. D., Lynch, J. C., Vose, J., Armitage, J. O., Smeland, E. B., Kvaloy, S., Holte, H., Delabie, J., Campo, E., ... Staudt, L. M. (2003). Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. Journal of Experimental Medicine, 198(6), 851-862. https://doi.org/10.1084/jem.20031074