p52 Activation in Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder/Diffuse Large B-Cell Lymphoma without BAFF-R Expression

Proust, Alexis; Rince, Patricia; Creidy, Rita; Lazure, Thierry; Joab, Irène; Garçon, Loïc; Fabrè, Monique; Guettier, Catherine; Raphaël, Martine

doi:10.1016/j.ajpath.2011.07.003

Cited by 3 publications

(1 citation statement)

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“…Comprehensive immunohistochemical analysis of all five NF‐κB sub‐compounds has been performed in only few studies so far . The importance of NF‐κB signalling in relation to the EBV status has been analysed in a study of similar size on DLBCL‐PTLD , yet that study only focused on p50 and p52. Our observed link between EBV infection in cluster 2 (mainly EBV latency type I and II cases) and compounds of the non‐canonical NF‐κB pathway has been reported: in the provisional entity of another immunodysregulation‐related DLBCL, ‘EBV‐positive DLBCL of the elderly’, an activity of the NF‐κB pathway has been shown and validated in vitro .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive phenotypic characterization of PTLD reveals potential reliance on EBV or NF‐κB signalling instead of B‐cell receptor signalling

Menter

Dickenmann

Juškevičius

et al. 2016

Hematological Oncology

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Post-transplant lymphoproliferative disorders (PTLD) are a major problem in transplant medicine. So far, the insights into pathogenesis and potentially druggable pathways in PTLD remain scarce. We investigated a cohort of PTLD patients, consisting of both polymorphic (n = 3) and monomorphic (n = 19) B-cell lymphoproliferations. Several signalling pathways, cell of origin of PTLD and their relation to viruses were analysed by immunohistochemistry and in situ hybridization. Most PTLD were of activated B-cell origin. Two-thirds of cases showed an Epstein-Barr virus (EBV) infection of the neoplastic cells. NF-κB signalling components were present in the majority of cases, except for EBV-infected cases with latency type III lacking CD19 and upstream B-cell signalling constituents. Proteins involved in B-cell receptor signalling like Bruton tyrosine kinase were only present in a minority of cases. Phosphoinositide 3-kinase (PI3K) was expressed in 94% of cases and the druggable PI3K class 1 catalytic subunit p110 in 76%, while proteins of other signalling transduction pathways were expressed only in single cases. Unsupervised cluster analysis revealed three distinct subgroups: (i) related to EBV infection, mainly latency type III and mostly lacking CD19, upstream B-cell signalling and NF-κB constituents; (ii) mostly related to EBV infection with expression of the alternative NF-κB pathway compound RelB, CD10, and FOXP1 or MUM1; and finally, (iii) mostly unrelated to virus infection with expression of the classic NF-κB pathway compound p65. EBV and NF-κB are important drivers in PTLD in contrast to B-cell receptor signalling. The main signal transduction pathway is related to PI3K. This links PTLD to other subgroups of EBV-related lymphomas, highlighting also new potential treatment approaches. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%