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An alternative way to look at diffuse large B-cell lymphoma : the impact of frequent engagement of ReIB NF-κB subunit on cell survival and patient outcome

Abstract : NF-κB transcription factors play critical role in cell proliferation, cell survival and the physiopathology of numerous cancers. Deregulation of the classical NF-κB pathway is known to be involved in at least the ABC subset of diffuse large B-cell lymphoma (DLBCL). However, the activation status of RelB NF-κB alternative pathway subunit and its role remain unclear. We have demonstrated a frequent engagement of RelB in human DLBCL-derived cell lines. RelB activation protected cells from DNA damage and apoptosis induced by doxorubicin, the main drug in DLBCL treatment. RelB also controlled the expression of the anti-apoptotic protein cIAP2. In a cohort of 66 de novo DLBCL patients, we have directly assessed the DNA binding activity of all NF-κB subunits by EMSA coupled with supershift. RelB activation was present in 66.6% of cases regardless of ABC or GCB classification and was an independent predictor of worse outcome. RelB activation status by EMSA allowed the definition of a RelB gene expression signature that was able to confirm RelB’s negative impact on patient outcome when extended to a larger cohort. Altogether, our study indicates that RelB is a potential new biomarker for DLBCL and sheds light on its important role in DLBCL cell biology.
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Davi Moreira Collares. An alternative way to look at diffuse large B-cell lymphoma : the impact of frequent engagement of ReIB NF-κB subunit on cell survival and patient outcome. Cellular Biology. Université Sorbonne Paris Cité, 2019. English. ⟨NNT : 2019USPCB019⟩. ⟨tel-02476412⟩

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