{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:03:50Z","timestamp":1753884230657,"version":"3.41.2"},"reference-count":38,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009857","name":"Regeneron Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009857","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small-animal models. Here, we demonstrate that IL-15 is a critical CTCL growth factor. Importantly, an immunodeficient knock-in mouse model genetically engineered to express human IL-15 uniquely supported the growth of SS patient samples relative to conventional immunodeficient mouse strains. SS patient-derived xenograft (PDX) models recapacitated key pathological features of the human disease, including skin infiltration and spread of leukemic cells to the periphery, and maintained the dependence on human IL-15 upon serial in vivo passaging. Detailed molecular characterization of the engrafted cells by single-cell transcriptomic analysis revealed congruent neoplastic gene expression signatures but distinct clonal engraftment patterns. Overall, we document an important dependence of Sezary cell survival and proliferation on IL-15 signaling and the utility of immunodeficient humanized IL-15 mice as hosts for SS \u2013 and potentially other T and NK cell-derived hematologic malignancies \u2013 PDX model generation. Furthermore, these studies advocate the thorough molecular understanding of the resultant PDX models to maximize their translational impact.<\/jats:p>","DOI":"10.1242\/dmm.050190","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T07:55:33Z","timestamp":1695023733000},"source":"Crossref","is-referenced-by-count":2,"title":["Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice"],"prefix":"10.1242","volume":"16","author":[{"given":"Jie","family":"Gao","sequence":"first","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shumei","family":"Ren","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6856-5006","authenticated-orcid":false,"given":"Gabrielle","family":"Choonoo","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoying","family":"Chen","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davor","family":"Frleta","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhong","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-1546","authenticated-orcid":false,"given":"Namita","family":"Gupta","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prachi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelekan","family":"Oyejide","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-6943","authenticated-orcid":false,"given":"Gurinder S.","family":"Atwal","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Macdonald","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Murphy","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-4225","authenticated-orcid":false,"given":"Frank","family":"Kuhnert","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc. , Tarrytown, NY 10591 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"2023101308251444400_DMM050190C1","doi-asserted-by":"publisher","first-page":"365","DOI":"10.3390\/v15020365","article-title":"Human hematopoietic stem cell engrafted IL-15 transgenic NSG mice support robust NK cell responses and sustained HIV-1 infection","volume":"15","author":"Abeynaike","year":"2023","journal-title":"Viruses"},{"key":"2023101308251444400_DMM050190C2","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1038\/nm.3962","article-title":"Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma","volume":"21","author":"Adachi","year":"2015","journal-title":"Nat. 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