CYCLON and NPM1 Cooperate within an Oncogenic Network Predictive of R-CHOP Response in DLBCL
| العنوان: | CYCLON and NPM1 Cooperate within an Oncogenic Network Predictive of R-CHOP Response in DLBCL |
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| المؤلفون: | Tatiana Raskovalova, Edwige Col, Caroline Algrin, Marie-Christine Jacob, Cyril Fournier, Anne McLeer, Anouk Emadali, Samuel Duley, Romain Aucagne, Antonin Bouroumeau, Mary Callanan, Claire Vettier, Hervé Sartelet, Christine Lefebvre, Patricia Betton-Fraisse, Thierry Bonnefoix, Yohann Couté, Lucile Bussot, Andrea Garcìa-Sandoval, Sieme Hamaidia, Annie Adrait, Simon Chevalier, Laurence David-Boudet, Anna Bergan-Dahl, Remy Gressin, Sylvain Carras |
| المساهمون: | Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier Universitaire [Grenoble] (CHU), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut Daniel Hollard [Grenoble], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Bruley, Christophe |
| المصدر: | Cancers Cancers, 2021, 13 (23), pp.5900. ⟨10.3390/cancers13235900⟩ Cancers, Vol 13, Iss 5900, p 5900 (2021) Cancers; Volume 13; Issue 23; Pages: 5900 |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, NPM1, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Article, immune system diseases, Internal medicine, hemic and lymphatic diseases, medicine, CYCLON, nucleolus, R-CHOP, prognosis, R-IPI, Nuclear protein, Adverse effect, RC254-282, Rna processing, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Immunotherapy, medicine.disease, Lymphoma, [SDV] Life Sciences [q-bio], Immunohistochemistry, business |
| الوصف: | Simple Summary CYCLON is a nuclear protein, which has been associated with disease progression and treatment resistance in DLBCL, the most common form of aggressive B-cell lymphoma, but also represents a predictive factor of refractory disease and relapse for immuno-chemotherapy-treated DLBCL patients. The molecular mechanisms related to this unstructured protein remain largely uncharacterized. Here, we performed a mass-spectrometry-based identification of the CYCLON protein interactome that suggested it could exert nucleolar functions related to cell proliferation. Among the CYCLON oncogenic network, we performed an immunohistochemical evaluation of the multi-functional nucleolar protein NPM1 in a DLBCL cohort and showed that CYCLON/NPM1 concomitant expression delineates a poor prognosis subgroup of patients. Multivariate survival analyses demonstrated that specific sub-cellular localizations of CYCLON and NPM1 represent independent novel predictors specifically associated with refractory DLBCL. Abstract R-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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c893b19d2eb4aa502b8fd351c130cce3Test http://europepmc.org/articles/PMC8656558Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c893b19d2eb4aa502b8fd351c130cce3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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