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.
journal_name
Bloodjournal_title
Bloodauthors
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,Spier CM,Fisher RI,Delabie J,Rosenwald A,Staudt LM,Grogan TMdoi
10.1182/blood-2003-07-2365subject
Has Abstractpub_date
2004-06-01 00:00:00pages
4251-8issue
11eissn
0006-4971issn
1528-0020pii
2003-07-2365journal_volume
103pub_type
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