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Les lymphomes B diffus à grandes cellules de type activé : rôle de NF-κB et c-Myc.

Abstract : Not only Burkitt lymphoma (BL) with the translocation of MYC, but also diffuse large B-cell lymphoma (DLBCL) by other mechanisms (mutation, amplification, promoter dysregulation…) are associated with dysregulation of c-Myc, the master transcription factor for proliferation. DLBCL’s are classified in two subgroups: “Germinal center B-cell” (GCB) without and “activated B-cell” (ABC) with constitutive NF-κB activation. This constitutive activation of NF-κB can be the result of genetic alterations (MYD88, A20, TRAF2, and TRAF5) or the activation of B-cell receptor or CD40. These features raise the question of the synergy of action between NF-κB and c-Myc in ABC-DLBCL. We analyzed the effect of a continuous activation of c-Myc in a context of over-activation of NF-κB by several inductors. Our results show that overexpression of c-Myc in the context of induction of NF-κB, i) by EBV latency III program, provides a selective advantage to those cells (gene expression in favor of a high metabolism, intense proliferation and protection against apoptosis), ii) by TLR9 (in vivo and in vitro model) increases the survival and proliferation of B lymphocytes of λc-Myc mice (increase of activated B cells, splenomegaly, increased B cells proliferation, modification of tumor microenvironment), and iii) by CD40, induces a very aggressive B lymphomagenesis in CD40/Myc double transgenic mice, the tumors have a phenotype close to ABC-DLBCL. These results suggest that c-Myc is an NF-κB co-transforming event in aggressive lymphomas with an activated phenotype by NF-κB, such as ABC-DLBCL.
Mots-clés : NF-κB C-Myc DLBCL TLR9
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Submitted on : Wednesday, July 11, 2018 - 10:06:13 AM
Last modification on : Sunday, June 26, 2022 - 1:21:59 PM
Long-term archiving on: : Friday, October 12, 2018 - 3:55:46 PM


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  • HAL Id : tel-01835000, version 1



Nicolas Arnaud. Les lymphomes B diffus à grandes cellules de type activé : rôle de NF-κB et c-Myc.. Médecine humaine et pathologie. Université de Limoges, 2017. Français. ⟨NNT : 2017LIMO0105⟩. ⟨tel-01835000⟩



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