Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: A follow-up study from the Leukemia and Lymphoma Molecular Profiling Project

Lisa M Rimsza, Robin A. Roberts, Thomas P Miller, Joseph M. Unger, Michael LeBlanc, Rita M. Braziel, Dennis D. Weisenberger, Wing C. Chan, H. Konrad Muller-Hermelink, Elaine S. Jaffe, Randy D. Gascoyne, Elias Campo, Deborah A. Fuchs, Catherine S Perry, Richard I. Fisher, Jan Delabie, Andreas Rosenwald, Louis M. Staudt, Thomas M. Grogan

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Abstract

The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression "signatures" were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA) which correlated with better survival. We further analyzed the effects of HLA-DRA on survival and correlated gene expression with protein status and tumor-infiltrating lymphocytes. The 5-year overall survival was 24% in the lowest 10% of HLA-DRA expression, 37% in the 10% to 25% group, 50% in the 25% to 50% group, and 55% for patients in the highest 50%. Further analysis demonstrated that the hazard ratio of death was a nonlinear function of HLA-DRA expression. Adjustment for the International Prognostic Index did not alter the impact of HLA-DRA on survival. Other MHC class II genes were found to predict survival similarly. Microarray HLA-DRA expression correlated with the presence or absence of human leukocyte antigen-DR (HLA-DR) protein in 20 of 22 cases assessed. Fewer tumor-infiltrating CD8+ T cells were detected in MHC class II-negative cases compared with positive cases (2.8% versus 11.0%; P = .001), supporting the hypothesis that loss of tumor immunosurveillance has a devastating effect on patient outcome in DLBCL.

Original languageEnglish (US)
Pages (from-to)4251-4258
Number of pages8
JournalBlood
Volume103
Issue number11
DOIs
StatePublished - Jun 1 2004

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HLA-DR alpha-Chains
Immunologic Monitoring
MHC Class II Genes
Lymphoma, Large B-Cell, Diffuse
Major Histocompatibility Complex
Tumors
Lymphoma
Leukemia
Cells
Gene Expression
Survival
Neoplasms
Proteins
Microarrays
Gene expression
Genes
Tumor-Infiltrating Lymphocytes
T-cells
Lymphocytes
Microarray Analysis

ASJC Scopus subject areas

  • Hematology

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Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors : A follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. / Rimsza, Lisa M; Roberts, Robin A.; Miller, Thomas P; Unger, Joseph M.; LeBlanc, Michael; Braziel, Rita M.; Weisenberger, Dennis D.; Chan, Wing C.; Muller-Hermelink, H. Konrad; Jaffe, Elaine S.; Gascoyne, Randy D.; Campo, Elias; Fuchs, Deborah A.; Perry, Catherine S; Fisher, Richard I.; Delabie, Jan; Rosenwald, Andreas; Staudt, Louis M.; Grogan, Thomas M.

In: Blood, Vol. 103, No. 11, 01.06.2004, p. 4251-4258.

Research output: Contribution to journalArticle

Rimsza, LM, Roberts, RA, Miller, TP, Unger, JM, LeBlanc, M, Braziel, RM, Weisenberger, DD, Chan, WC, Muller-Hermelink, HK, Jaffe, ES, Gascoyne, RD, Campo, E, Fuchs, DA, Perry, CS, Fisher, RI, Delabie, J, Rosenwald, A, Staudt, LM & Grogan, TM 2004, 'Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: A follow-up study from the Leukemia and Lymphoma Molecular Profiling Project', Blood, vol. 103, no. 11, pp. 4251-4258. https://doi.org/10.1182/blood-2003-07-2365
Rimsza, Lisa M ; Roberts, Robin A. ; Miller, Thomas P ; Unger, Joseph M. ; LeBlanc, Michael ; Braziel, Rita M. ; Weisenberger, Dennis D. ; Chan, Wing C. ; Muller-Hermelink, H. Konrad ; Jaffe, Elaine S. ; Gascoyne, Randy D. ; Campo, Elias ; Fuchs, Deborah A. ; Perry, Catherine S ; Fisher, Richard I. ; Delabie, Jan ; Rosenwald, Andreas ; Staudt, Louis M. ; Grogan, Thomas M. / Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors : A follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. In: Blood. 2004 ; Vol. 103, No. 11. pp. 4251-4258.
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AU - Rimsza, Lisa M

AU - Roberts, Robin A.

AU - Miller, Thomas P

AU - Unger, Joseph M.

AU - LeBlanc, Michael

AU - Braziel, Rita M.

AU - Weisenberger, Dennis D.

AU - Chan, Wing C.

AU - Muller-Hermelink, H. Konrad

AU - Jaffe, Elaine S.

AU - Gascoyne, Randy D.

AU - Campo, Elias

AU - Fuchs, Deborah A.

AU - Perry, Catherine S

AU - Fisher, Richard I.

AU - Delabie, Jan

AU - Rosenwald, Andreas

AU - Staudt, Louis M.

AU - Grogan, Thomas M.

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