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

Hematological Oncology
Thomas MenterAlexandar Tzankov

Abstract

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 ...Continue Reading

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Citations

May 7, 2019·Applied Immunohistochemistry & Molecular Morphology : AIMM·William SterlacciAlexandar Tzankov
Jun 25, 2020·Life Science Alliance·Donal McHughChristian Münz
Apr 19, 2017·British Journal of Haematology·Thomas MenterKikkeri N Naresh

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