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 Montserrat & 18 others Armando 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

776 Citations (Scopus)

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

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Lymphoma, Large B-Cell, Diffuse
B-Cell Lymphoma
Hodgkin Disease
Gene Expression Profiling
Transcriptional Activation
Genes
Lymphoma
Thorax
Survival Rate
T-Lymphocytes
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. / Rosenwald, Andreas; Wright, George; Leroy, Karen; Yu, Xin; Gaulard, Philippe; Gascoyne, Randy D.; Chan, Wing C.; Zhao, Tong; Haioun, Corinne; Greiner, Timothy C.; Weisenburger, Dennis D.; Lynch, James C.; Vose, Julie; Armitage, James O.; Smeland, Erlend B.; Kvaloy, Stein; Holte, Harald; Delabie, Jan; Campo, Elias; Montserrat, Emili; Lopez-Guillermo, Armando; Ott, German; Muller-Hermelink, H. Konrad; Connors, Joseph M.; Braziel, Rita; Grogan, Thomas M.; Fisher, Richard I.; Miller, Thomas P.; LeBlanc, Michael; Chiorazzi, Michael; Zhao, Hong; Yang, Liming; Powell, John; Wilson, Wyndham H.; Jaffe, Elaine S.; Simon, Richard; Klausner, Richard D.; Staudt, Louis M.

In: Journal of Experimental Medicine, Vol. 198, No. 6, 15.09.2003, p. 851-862.

Research output: Contribution to journalArticle

Rosenwald, A, Wright, G, Leroy, K, Yu, X, Gaulard, P, Gascoyne, RD, Chan, WC, Zhao, T, Haioun, C, Greiner, TC, Weisenburger, DD, Lynch, JC, Vose, J, Armitage, JO, Smeland, EB, Kvaloy, S, Holte, H, Delabie, J, Campo, E, Montserrat, E, Lopez-Guillermo, A, Ott, G, Muller-Hermelink, HK, Connors, JM, Braziel, R, Grogan, TM, Fisher, RI, Miller, TP, LeBlanc, M, Chiorazzi, M, Zhao, H, Yang, L, Powell, J, Wilson, WH, Jaffe, ES, Simon, R, Klausner, RD & Staudt, LM 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, vol. 198, no. 6, pp. 851-862. https://doi.org/10.1084/jem.20031074
Rosenwald, Andreas ; Wright, George ; Leroy, Karen ; Yu, Xin ; Gaulard, Philippe ; Gascoyne, Randy D. ; Chan, Wing C. ; Zhao, Tong ; Haioun, Corinne ; Greiner, Timothy C. ; Weisenburger, Dennis D. ; Lynch, James C. ; Vose, Julie ; Armitage, James O. ; Smeland, Erlend B. ; Kvaloy, Stein ; Holte, Harald ; Delabie, Jan ; Campo, Elias ; Montserrat, Emili ; Lopez-Guillermo, Armando ; Ott, German ; Muller-Hermelink, H. Konrad ; Connors, Joseph M. ; Braziel, Rita ; Grogan, Thomas M. ; Fisher, Richard I. ; Miller, Thomas P. ; LeBlanc, Michael ; Chiorazzi, Michael ; Zhao, Hong ; Yang, Liming ; Powell, John ; Wilson, Wyndham H. ; Jaffe, Elaine S. ; Simon, Richard ; Klausner, Richard D. ; Staudt, Louis M. / Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. In: Journal of Experimental Medicine. 2003 ; Vol. 198, No. 6. pp. 851-862.
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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.",
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T1 - Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma

AU - Rosenwald, Andreas

AU - Wright, George

AU - Leroy, Karen

AU - Yu, Xin

AU - Gaulard, Philippe

AU - Gascoyne, Randy D.

AU - Chan, Wing C.

AU - Zhao, Tong

AU - Haioun, Corinne

AU - Greiner, Timothy C.

AU - Weisenburger, Dennis D.

AU - Lynch, James C.

AU - Vose, Julie

AU - Armitage, James O.

AU - Smeland, Erlend B.

AU - Kvaloy, Stein

AU - Holte, Harald

AU - Delabie, Jan

AU - Campo, Elias

AU - Montserrat, Emili

AU - Lopez-Guillermo, Armando

AU - Ott, German

AU - Muller-Hermelink, H. Konrad

AU - Connors, Joseph M.

AU - Braziel, Rita

AU - Grogan, Thomas M.

AU - Fisher, Richard I.

AU - Miller, Thomas P.

AU - LeBlanc, Michael

AU - Chiorazzi, Michael

AU - Zhao, Hong

AU - Yang, Liming

AU - Powell, John

AU - Wilson, Wyndham H.

AU - Jaffe, Elaine S.

AU - Simon, Richard

AU - Klausner, Richard D.

AU - Staudt, Louis M.

PY - 2003/9/15

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N2 - 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.

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KW - Microarray

KW - Outcome prediction

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