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Title: Gene expression profiling reveals clear differences between EBV-positive and EBV-negative posttransplant lymphoproliferative disorders
Authors: Morscio, Julie * ×
Dierickx, Daan *
Finalet Ferreiro, Julio
Herreman, An
Van Loo, Peter
Bittoun, Emilie
Verhoef, Gregor
Matthys, Patrick
Cools, Jan
Wlodarska, Iwona
De Wolf-Peeters, Chris
Sagaert, Xavier
Tousseyn, Thomas #
Issue Date: May-2013
Publisher: Munksgaard International Publishers
Series Title: American Journal of Transplantation vol:13 issue:5 pages:1305-1316
Abstract: Posttransplant patients are at risk of developing a potentially life-threatening posttransplantation lymphoproliferative disorder (PTLD), most often of diffuse large B cell lymphoma (DLBCL) morphology and associated with Epstein-Barr Virus (EBV) infection. The aim of this study was to characterize the clinicopathological and molecular-genetic characteristics of posttransplant DLBCL and to elucidate whether EBV(+) and EBV(-) posttransplant DLBCL are biologically different. We performed gene expression profiling studies on 48 DLBCL of which 33 arose posttransplantation (PT-DLBCL; 72% EBV+) and 15 in immunocompetent hosts (IC-DLBCL; none EBV+). Unsupervised hierarchical analysis showed clustering of samples related to EBV-status rather than immune status. Except for decreased T cell signaling these cases were inseparable from EBV(-) IC-DLBCL. In contrast, a viral response signature clearly segregated EBV(+) PT-DLBCL from EBV(-) PT-DLBCL and IC-DLBCL cases that were intermixed. The broad EBV latency profile (LMP1+/EBNA2+) was expressed in 59% of EBV(+) PT-DLBCL and associated with a more elaborate inflammatory response compared to intermediate latency (LMP1+/EBNA2-). Inference analysis revealed a role for innate and tolerogenic immune responses (including VSIG4 and IDO1) in EBV(+) PT-DLBCL. In conclusion we can state that the EBV signature is the most determining factor in the pathogenesis of EBV(+) PT-DLBCL.
URI: 
ISSN: 1600-6135
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Genetics of Malignant Disorders
Laboratory of Immunobiology (Rega Institute)
Laboratory of Experimental Hematology (+)
Department of Human Genetics - miscellaneous
Organ Systems (+)
Translational Cell & Tissue Research
Human Genome Laboratory
Laboratory of Molecular Biology of Leukemia
* (joint) first author
× corresponding author
# (joint) last author

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