Study of mechanisms involved in the resistance to apoptosis of cells infected with the Epstein-Barr virus and development of new therapeutic strategies for treatment of B lymphomas
type: Dataset
description: - Résumé en anglais : Our team is working on the mechanisms of apoptosis induced by nutlin-3, a small molecule which binds to MDM2 and activates p53, in different lymphomas associated with Epstein-Barr virus such as Burkitt lymphoma (BL) or Post-transplant lymphoproliferative disorder (PTLD). Our results show that nutlin-3 strongly induce apoptosis in EBV (-) cells whereas EBV (+) latency III cells are much more resistant. The aim of my PhD project was to study the mechanisms involved in the resistance of EBV (+) latency III cells to apoptosis and to develop new therapeutic strategies to bypass these mechanisms. A transcriptomic analysis was realized after treatment with nutlin-3 of two cell lines which only differs by their EBV status. Based on the results obtained, a study was performed which allow us to show that: 1) autophagy is induced after nutlin-3 treatment in EBV (+) latency III cells; 2) these cells strongly expressed beclin-1 and present a constitutively high level of autophagy; 3) autophagy is involved in the resistance of apoptosis observed in these cells. Furthermore, our results demonstrate that Bcl-2 also contributes to the resistance of EBV (+) latency III cells and that treatment with ABT-737, a Bcl-2 inhibitor, restores their susceptibility to nutlin-3 treatment. We thus assessed the efficiency of this compound in vivo, in monotherapy or associated with conventional treatments (Cyclophosphamide for BL and Rituximab for PTLD). Results obtained during these pre-clinical studies show that: 1) ABT-737 reduces tumor growth and increase the overall survival of mice xenografted with a lymphoblastoïd cell line (LCL, used as a model for PTLD studies) but has no effects on mice xenografed with BL cell lines; 2) the association ABT-737/Cyclophosphamide reduces tumor growth during treatment but doesn’t improve the overall survival of mice xenografed with BL cell lines; 3) the association ABT-737/Rituximab is very efficient and induces 70% of complete remissio…
landing page: https://theses.hal.science/tel-00767146
identifier: NNT: 2012PA11T054
keyword: abt-737
keyword: apoptose
keyword: apoptosis
keyword: autophagie
keyword: autophagy
keyword: bcl-2
keyword: burkitt-lymphome
keyword: ebv
keyword: infoeu-reposemanticsdoctoralthesis
keyword: lymphome-de-burkitt
keyword: lymphomes-post-transplants
keyword: nutlin-3
keyword: nutline-3
keyword: post-transplant-lymphoproliferative-disorder
keyword: sdvbclife-sciences-q-biocellular-biology
keyword: theses
issued: 2026-05-30T04:50:13.785666
modified: 2026-05-30T04:50:13.785677
language: fr
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Study of mechanisms involved in the resistance to apoptosis of cells infected with the Epstein-Barr virus and development of new therapeutic strategies for treatment of B lymphomas
type: Distribution
format: HTML
access URL: https://theses.hal.science/tel-00767146
issued: 2026-05-30T04:50:13.904792
modified: 2026-05-30T04:50:13.705285