{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:49:58Z","timestamp":1785412198773,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,2]]},"group-title":"Pathology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["CA228524"],"award-info":[{"award-number":["CA228524"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Diffuse large B-cell lymphoma (DLBCL) represents 30\u201340% of non-Hodgkin lymphoma cases and is curable in &gt;60% of patients; however, approximately one-third ultimately relapse. Although prior studies in normal B cells and lymphoma models implicate p73 in B-cell lymphomagenesis, the functional role of individual p73 isoforms in DLBCL remains poorly defined. TP73, a TP53 family member located on chromosome 1p36, encodes both transcriptionally active (TAp73) and dominant-negative (\u0394Np73) isoforms that differentially regulate apoptosis and proliferation. In this study, we characterized p73 locus alterations, isoform-specific expression patterns, and their biological relevance in DLBCL. Chromosomal analysis revealed disruption of the 1p36 locus\u2014predominantly via heterozygous deletion\u2014in 35% of patient samples, which significantly correlated with elevated \u0394Np73 expression. Immunohistochemical profiling demonstrated a positive association between TAp73 and cleaved caspase-3, and between \u0394Np73 and Ki-67. Conversely, TAp73 expression negatively correlated with the anti-apoptotic proteins Bcl-2 and Bcl-6. Functional studies in DLBCL cell lines further confirmed that TAp73 enhances sensitivity to serum deprivation and doxorubicin, whereas \u0394Np73 overexpression promotes survival and chemoresistance. Together, these findings identify p73 isoform imbalance as a key contributor to DLBCL pathogenesis and therapeutic response, highlighting \u0394Np73 as a potential biomarker of aggressive disease and treatment resistance, and TAp73 as a tumor-suppressive axis warranting further investigation.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, yet relapse remains a major challenge. The p73 gene produces two key isoforms with opposing functions: TAp73, which promotes apoptosis, and \u0394Np73, which inhibits cell death and supports tumor growth. In DLBCL samples, 1p36 chromosomal disruption occurred in 35% of cases and was associated with elevated \u0394Np73. TAp73 expression correlated with apoptosis markers, whereas \u0394Np73 correlated with proliferation. Functional studies showed TAp73 sensitizes DLBCL cells to stress and chemotherapy, while \u0394Np73 enhances resistance. These findings highlight \u0394Np73 as a potential biomarker and therapeutic target in DLBCL.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.28.702345","type":"posted-content","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:35:14Z","timestamp":1770042914000},"source":"Crossref","is-referenced-by-count":0,"title":["Isoform-Specific Functions of p73 Drive Survival and Chemoresistance in Diffuse Large B-Cell Lymphoma"],"prefix":"10.64898","author":[{"given":"Hesham M.","family":"Hassan","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine, King Khalid University, Saudi Arabia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Varney","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis D.","family":"Weisenburger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1317-3520","authenticated-orcid":false,"given":"Rakesh K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavana J.","family":"Dave","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"10","key":"2026033101400914000_2026.01.28.702345v2.1","first-page":"e250048","article-title":"NCCN Guidelines\u00ae Insights: B-Cell Lymphomas 3.2025: Featured Updates to the NCCN Guidelines","volume":"23","year":"2025","journal-title":"Journal of the National Comprehensive Cancer Network"},{"key":"2026033101400914000_2026.01.28.702345v2.2","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200109000-00003"},{"key":"2026033101400914000_2026.01.28.702345v2.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-293050"},{"issue":"9","key":"2026033101400914000_2026.01.28.702345v2.4","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1007\/s00277-024-05880-z","article-title":"Advances in biology, diagnosis and treatment of DLBCL","volume":"103","year":"2024","journal-title":"Ann Hematol"},{"issue":"5","key":"2026033101400914000_2026.01.28.702345v2.5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/j.seminhematol.2023.11.006","article-title":"Biological heterogeneity in diffuse large B-cell lymphoma","volume":"60","year":"2023","journal-title":"Semin Hematol"},{"issue":"3","key":"2026033101400914000_2026.01.28.702345v2.6","doi-asserted-by":"crossref","first-page":"110713","DOI":"10.1016\/j.celrep.2022.110713","article-title":"A single-cell atlas of diffuse large B cell lymphoma","volume":"39","year":"2022","journal-title":"Cell reports"},{"key":"2026033101400914000_2026.01.28.702345v2.7","doi-asserted-by":"publisher","DOI":"10.1182\/BLOOD.2022015854"},{"key":"2026033101400914000_2026.01.28.702345v2.8","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003535"},{"key":"2026033101400914000_2026.01.28.702345v2.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801445"},{"key":"2026033101400914000_2026.01.28.702345v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"2026033101400914000_2026.01.28.702345v2.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012914"},{"issue":"3","key":"2026033101400914000_2026.01.28.702345v2.12","first-page":"166","article-title":"[Classification of aggressive B-cell lymphomas : News and open questions]","volume":"44","year":"2023","journal-title":"Pathologie (Heidelb)"},{"key":"2026033101400914000_2026.01.28.702345v2.13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.09.137"},{"key":"2026033101400914000_2026.01.28.702345v2.14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.9277"},{"key":"2026033101400914000_2026.01.28.702345v2.15","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2012.0155"},{"key":"2026033101400914000_2026.01.28.702345v2.16","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds517"},{"issue":"2","key":"2026033101400914000_2026.01.28.702345v2.17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.blre.2015.08.002","article-title":"Genomic signatures in B-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?","volume":"30","year":"2016","journal-title":"Blood Rev"},{"key":"2026033101400914000_2026.01.28.702345v2.18","doi-asserted-by":"crossref","unstructured":"Hassan HM , Dave BJ , Singh RK . 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