{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:22:46Z","timestamp":1787498566370,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Advanced Research Activities in Biomedical and Agro-alimentary Technologies","award":["MIS 5002469"],"award-info":[{"award-number":["MIS 5002469"]}]},{"name":"Advanced Research Activities in Biomedical and Agro-alimentary Technologies","award":["NSRF 2014\u20132020"],"award-info":[{"award-number":["NSRF 2014\u20132020"]}]},{"name":"Advanced Research Activities in Biomedical and Agro-alimentary Technologies","award":["MIS-5033021"],"award-info":[{"award-number":["MIS-5033021"]}]},{"name":"Competitiveness, Entrepreneurship and Innovation","award":["MIS 5002469"],"award-info":[{"award-number":["MIS 5002469"]}]},{"name":"Competitiveness, Entrepreneurship and Innovation","award":["NSRF 2014\u20132020"],"award-info":[{"award-number":["NSRF 2014\u20132020"]}]},{"name":"Competitiveness, Entrepreneurship and Innovation","award":["MIS-5033021"],"award-info":[{"award-number":["MIS-5033021"]}]},{"name":"Reinforcement of Postdoctoral Researchers\u20142nd Cycle","award":["MIS 5002469"],"award-info":[{"award-number":["MIS 5002469"]}]},{"name":"Reinforcement of Postdoctoral Researchers\u20142nd Cycle","award":["NSRF 2014\u20132020"],"award-info":[{"award-number":["NSRF 2014\u20132020"]}]},{"name":"Reinforcement of Postdoctoral Researchers\u20142nd Cycle","award":["MIS-5033021"],"award-info":[{"award-number":["MIS-5033021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mantle cell lymphoma (MCL) is a rare, incurable, and aggressive B-cell non-Hodgkin lymphoma (NHL). Early MCL diagnosis and treatment is critical and puzzling due to inter\/intra-tumoral heterogeneity and limited understanding of the underlying molecular mechanisms. We developed and applied a multifaceted analysis of selected publicly available transcriptomic data of well-defined MCL stages, integrating network-based methods for pathway enrichment analysis, co-expression module alignment, drug repurposing, and prediction of effective drug combinations. We demonstrate the \u201cbutterfly effect\u201d emerging from a small set of initially differentially expressed genes, rapidly expanding into numerous deregulated cellular processes, signaling pathways, and core machineries as MCL becomes aggressive. We explore pathogenicity-related signaling circuits by detecting common co-expression modules in MCL stages, pointing out, among others, the role of VEGFA and SPARC proteins in MCL progression and recommend further study of precise drug combinations. Our findings highlight the benefit that can be leveraged by such an approach for better understanding pathobiology and identifying high-priority novel diagnostic and prognostic biomarkers, drug targets, and efficacious combination therapies against MCL that should be further validated for their clinical impact.<\/jats:p>","DOI":"10.3390\/ijms25137298","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Insight into Mantle Cell Lymphoma Pathobiology, Diagnosis, and Treatment Using Network-Based and Drug-Repurposing Approaches"],"prefix":"10.3390","volume":"25","author":[{"given":"Georgia","family":"Orfanoudaki","sequence":"first","affiliation":[{"name":"Functional Proteomics and Systems Biology (FunPATh), Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, GR-54124 Thessaloniki, Greece"},{"name":"Institute of Molecular Biology and Biotechnology Foundation for Research and Technology\u2014Hellas, GR-70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Psatha","sequence":"additional","affiliation":[{"name":"Functional Proteomics and Systems Biology (FunPATh), Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, GR-54124 Thessaloniki, Greece"},{"name":"Institute of Molecular Biology and Biotechnology Foundation for Research and Technology\u2014Hellas, GR-70013 Heraklion, Greece"},{"name":"Laboratory of Medical Biology\u2014Genetics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1173-7705","authenticated-orcid":false,"given":"Michalis","family":"Aivaliotis","sequence":"additional","affiliation":[{"name":"Functional Proteomics and Systems Biology (FunPATh), Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, GR-54124 Thessaloniki, Greece"},{"name":"Institute of Molecular Biology and Biotechnology Foundation for Research and Technology\u2014Hellas, GR-70013 Heraklion, Greece"},{"name":"Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece"},{"name":"Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1182\/blood.2022015851","article-title":"The International Consensus Classification of Mature Lymphoid Neoplasms: A report from the Clinical Advisory Committee","volume":"140","author":"Campo","year":"2022","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.hoc.2020.05.002","article-title":"Molecular Pathogenesis of Mantle Cell Lymphoma","volume":"34","author":"Navarro","year":"2020","journal-title":"Hematol. 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