Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival

Robin A. Roberts, George Wright, Andreas R. Rosenwald, Marina A. Jaramillo, Thomas M. Grogan, Thomas P Miller, Yvette Frutiger, Wing C. Chan, Randy D. Gascoyne, German Ott, H. Konrad Muller-Hermelink, Louis M. Staudt, Lisa M Rimsza

Research output: Contribution to journalArticle

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Abstract

Loss of major histocompatibility class II (MHC II) expression in diffuse large B-cell lymphoma (DLBCL) correlates with worse outcome, possibly from decreased immunosurveillance. Primary mediastinal B-cell lymphoma (PMBCL) is a subtype of DLBCL which reportedly has frequent loss of MHC II proteins; however, PMBCL has better survival than DLBCL. To investigate this paradox, we used gene-expression profiling (GEP) data and immunohistochemistry to study expression of MHC II and its regulatory genes and to determine their relationship to PMBCL survival. We found that GEP levels correlated between MHC II genes and the transcriptional regulator MHC2TA but not other adjacent genes, implying that transcriptional regulation of MHC II in PMBCL was intact and that MHC II gene deletion was unlikely. MHC II average expression was lower than in certain subtypes of DLBCL; however, only 12% had complete loss of MHC II expression. Poor patient survival in PMBCL correlated with incremental decreases in MHC II expression. Although overall survival was better, survival of the lowest 10% of MHC II expressers was similarly poor in DLBCL and PMBCL. MHC II expression may define a therapeutic target in both these diseases.

Original languageEnglish (US)
Pages (from-to)311-318
Number of pages8
JournalBlood
Volume108
Issue number1
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

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MHC Class II Genes
Histocompatibility
B-Cell Lymphoma
Genes
Cells
Gene Expression
Survival
Lymphoma, Large B-Cell, Diffuse
Gene expression
Proteins
Gene Expression Profiling
Immunologic Monitoring
Gene Deletion
Regulator Genes
Cell Survival
Immunohistochemistry

ASJC Scopus subject areas

  • Hematology

Cite this

Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival. / Roberts, Robin A.; Wright, George; Rosenwald, Andreas R.; Jaramillo, Marina A.; Grogan, Thomas M.; Miller, Thomas P; Frutiger, Yvette; Chan, Wing C.; Gascoyne, Randy D.; Ott, German; Muller-Hermelink, H. Konrad; Staudt, Louis M.; Rimsza, Lisa M.

In: Blood, Vol. 108, No. 1, 01.07.2006, p. 311-318.

Research output: Contribution to journalArticle

Roberts, RA, Wright, G, Rosenwald, AR, Jaramillo, MA, Grogan, TM, Miller, TP, Frutiger, Y, Chan, WC, Gascoyne, RD, Ott, G, Muller-Hermelink, HK, Staudt, LM & Rimsza, LM 2006, 'Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival', Blood, vol. 108, no. 1, pp. 311-318. https://doi.org/10.1182/blood-2005-11-4742
Roberts, Robin A. ; Wright, George ; Rosenwald, Andreas R. ; Jaramillo, Marina A. ; Grogan, Thomas M. ; Miller, Thomas P ; Frutiger, Yvette ; Chan, Wing C. ; Gascoyne, Randy D. ; Ott, German ; Muller-Hermelink, H. Konrad ; Staudt, Louis M. ; Rimsza, Lisa M. / Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival. In: Blood. 2006 ; Vol. 108, No. 1. pp. 311-318.
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