CYCLON and NPM1 Cooperate within an Oncogenic Network Predictive of R-CHOP Response in DLBCL.
Antonin Bouroumeau, Lucile Bussot, Sieme Hamaidia, Andrea Garcìa-Sandoval, Anna Bergan-Dahl, Patricia Betton-Fraisse, Samuel Duley, Cyril Fournier, Romain Aucagne, Annie Adrait, Yohann Couté, Anne McLeer, Edwige Col, Laurence David-Boudet, Tatiana Raskovalova, Marie-Christine Jacob, Claire Vettier, Simon Chevalier, Sylvain Carras, Christine Lefebvre, Caroline Algrin, Rémy Gressin, Mary B Callanan, Hervé Sartelet, Thierry Bonnefoix, Anouk Emadali
Cancers 2021 Nov 24R-CHOP immuno-chemotherapy significantly improved clinical management of diffuse large B-cell lymphoma (DLBCL). However, 30-40% of DLBCL patients still present a refractory disease or relapse. Most of the prognostic markers identified to date fail to accurately stratify high-risk DLBCL patients. We have previously shown that the nuclear protein CYCLON is associated with DLBCL disease progression and resistance to anti-CD20 immunotherapy in preclinical models. We also recently reported that it also represents a potent predictor of refractory disease and relapse in a retrospective DLBCL cohort. However, only sparse data are available to predict the potential biological role of CYCLON and how it might exert its adverse effects on lymphoma cells. Here, we characterized the protein interaction network of CYCLON, connecting this protein to the nucleolus, RNA processing, MYC signaling and cell cycle progression. Among this network, NPM1, a nucleolar multi-functional protein frequently deregulated in cancer, emerged as another potential target related to treatment resistance in DLBCL. Immunohistochemistry evaluation of CYCLON and NPM1 revealed that their co-expression is strongly related to inferior prognosis in DLBCL. More specifically, alternative sub-cellular localizations of the proteins (extra-nucleolar CYCLON and pan-cellular NPM1) represent independent predictive factors specifically associated to R-CHOP refractory DLBCL patients, which could allow them to be orientated towards risk-adapted or novel targeted therapies.
Citation
Antonin Bouroumeau, Lucile Bussot, Sieme Hamaidia, Andrea Garcìa-Sandoval, Anna Bergan-Dahl, Patricia Betton-Fraisse, Samuel Duley, Cyril Fournier, Romain Aucagne, Annie Adrait, Yohann Couté, Anne McLeer, Edwige Col, Laurence David-Boudet, Tatiana Raskovalova, Marie-Christine Jacob, Claire Vettier, Simon Chevalier, Sylvain Carras, Christine Lefebvre, Caroline Algrin, Rémy Gressin, Mary B Callanan, Hervé Sartelet, Thierry Bonnefoix, Anouk Emadali. CYCLON and NPM1 Cooperate within an Oncogenic Network Predictive of R-CHOP Response in DLBCL. Cancers. 2021 Nov 24;13(23)
PMID: 34885010
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