c-Myc dysregulation is a co-transforming event for nuclear factor-κB activated B cells

Haematologica
Amandine DavidNathalie Faumont

Abstract

While c-Myc dysregulation is constantly associated with highly proliferating B-cell tumors, nuclear factor (NF)-κB addiction is found in indolent lymphomas as well as diffuse large B-cell lymphomas, either with an activated B-cell like phenotype or associated with the Epstein-Barr virus. We raised the question of the effect of c-Myc in B cells with NF-κB activated by three different inducers: Epstein-Barr virus-latency III program, TLR9 and CD40. Induction of c-Myc overexpression increased proliferation of Epstein-Barr virus-latency III immortalized B cells, an effect that was dependent on NF-κB. Results from transcriptomic signatures and functional studies showed that c-Myc overexpression increased Epstein-Barr virus-latency III-driven proliferation depending on NF-κB. In vitro, induction of c-Myc increased proliferation of B cells with TLR9-dependant activation of MyD88, with decreased apoptosis. In the transgenic λc-Myc mouse model with c-Myc overexpression in B cells, in vivo activation of MyD88 by TLR9 induced splenomegaly related to an increased synthesis phase (S-phase) entry of B cells. Transgenic mice with both continuous CD40 signaling in B cells and the λc-Myc transgene developed very aggressive lymphomas with charac...Continue Reading

Citations

Jun 19, 2018·PloS One·Isabele F MorettiSuely K N Marie
Aug 23, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Héloïse AuclairChantal Jayat-Vignoles
Oct 20, 2020·Infectious Agents and Cancer·J CharostadE Faghihloo

Methods Mentioned

BETA
electrophoretic mobility shift
flow cytometry
transfection

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