{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T02:17:13Z","timestamp":1769912233712,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5 P30 CA043703\u201032"],"award-info":[{"award-number":["5 P30 CA043703\u201032"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Angioimmunoblastic T\u2010cell lymphoma (AITL) is a rare and aggressive lymphoma with a poor prognosis. AITL is associated with Epstein\u2013Barr virus (EBV)\u2010positive B cells in most cases, suggesting a possible role for the virus in the pathobiology of AITL. Cell lines from AITL patients do not exist and models of human AITL are needed. We aim to establish such a model and use it for preclinical therapeutic evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary lymph node tissue from an AITL patient was used for tumor cell isolation and injection to NSG mice. The established patient\u2010derived xenograft (PDX) model was characterized by immunophenotyping, whole\u2010exome sequencing (WES), and T\/B\u2010cell receptor gene rearrangement studies. In vivo AITL PDX trials were performed with elotuzumab, romidepsin, and rituximab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An AITL PDX mouse model that includes a coexisting EBV+ B\u2010cell proliferation was established. We confirmed clonal identity of the engrafted T cells with the primary T\u2010lymphoma cells. WES on DNA from xenografted sorted T and B cells identified eight and three mutations previously reported in the COSMIC database, respectively. Primary tumor cells could be passaged serially in NSG mice with an increasing percentage of monoclonal B cells that mimic the human condition in which the clonal B\u2010cell component in some cases may mask an underling T\u2010cell lymphoma. In this PDX mouse study, single agent elotuzumab or rituximab significantly improved mice survival. Survival was further improved when elotuzumab or romidepsin was combined with rituximab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To our knowledge, this is the first molecular characterization of AITL model coexisting with associated EBV+ B cells, and use of such a PDX model for therapeutic evaluation of agents targeting both malignant T cells and B cells simultaneously.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jha2.1080","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T08:54:31Z","timestamp":1738054471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Angioimmunoblastic T\u2010cell lymphoma: Characterization of clonal T and B cells and a patient\u2010derived xenograft study of coexisting T\u2010 and B\u2010cell proliferation"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-3170","authenticated-orcid":false,"given":"Xiaoxian","family":"Zhao","sequence":"first","affiliation":[{"name":"Pathology and Lab Medicine Institute Cleveland Clinic  Cleveland Ohio USA"},{"name":"Wake Forest University School of Medicine  Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepa","family":"Jagadeesh","sequence":"additional","affiliation":[{"name":"Taussig Cancer Center Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4987-728X","authenticated-orcid":false,"given":"Juraj","family":"Bodo","sequence":"additional","affiliation":[{"name":"Pathology and Lab Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Durkin","sequence":"additional","affiliation":[{"name":"Pathology and Lab Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Lindner","sequence":"additional","affiliation":[{"name":"Taussig Cancer Center Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L.","family":"Ondrejka","sequence":"additional","affiliation":[{"name":"Pathology and Lab Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-4067","authenticated-orcid":false,"given":"Eric D.","family":"Hsi","sequence":"additional","affiliation":[{"name":"Pathology and Lab Medicine Institute Cleveland Clinic  Cleveland Ohio USA"},{"name":"Wake Forest University School of Medicine  Winston Salem North 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