{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:11:51Z","timestamp":1789269111492,"version":"build-2803163510"},"reference-count":72,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF14OC0012345"],"award-info":[{"award-number":["NNF14OC0012345"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Perturbation in JAK-STAT signaling has been reported in the pathogenesis of cutaneous T cell lymphoma (CTCL). JAK3 is predominantly associated with the intra-cytoplasmic part of IL-2R\u03b3c located in the plasma membrane of hematopoietic cells. Here we demonstrate that JAK3 is also ectopically expressed in the nucleus of malignant T cells. We detected nuclear JAK3 in various CTCL cell lines and primary malignant T cells from patients with S\u00e9zary syndrome, a leukemic variant of CTCL. Nuclear localization of JAK3 was independent of its kinase activity whereas STAT3 had a modest effect on nuclear JAK3 expression. Moreover, JAK3 nuclear localization was only weakly affected by blockage of nuclear export. An inhibitor of the nuclear export protein CRM1, Leptomycin B, induced an increased expression of SOCS3 in the nucleus, but only a weak increase in nuclear JAK3. Importantly, immunoprecipitation experiments indicated that JAK3 interacts with the nuclear protein POLR2A, the catalytic subunit of RNA Polymerase II. Kinase assays showed tyrosine phosphorylation of recombinant human Histone H3 by JAK3 in vitro\u2014an effect which was blocked by the JAK inhibitor (Tofacitinib citrate). In conclusion, we provide the first evidence of nuclear localization of JAK3 in malignant T cells. Our findings suggest that JAK3 may have a cytokine-receptor independent function in the nucleus of malignant T cells, and thus a novel non-canonical role in CTCL.<\/jats:p>","DOI":"10.3390\/cancers13020280","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T11:39:14Z","timestamp":1610624354000},"page":"280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["JAK3 Is Expressed in the Nucleus of Malignant T Cells in Cutaneous T Cell Lymphoma (CTCL)"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-5143","authenticated-orcid":false,"given":"Chella Krishna","family":"Vadivel","sequence":"first","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gluud","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8033-9474","authenticated-orcid":false,"given":"Sara","family":"Torres-Rusillo","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Boding","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"},{"name":"The Danish National Biobank, Statens Serum Institut, 2300 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Willerslev-Olsen","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7180-6384","authenticated-orcid":false,"given":"Terkild B.","family":"Buus","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tea Kirkegaard","family":"Nielsen","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7682-7678","authenticated-orcid":false,"given":"Jenny L.","family":"Persson","sequence":"additional","affiliation":[{"name":"Division of Basal Tumor Biology, Department of Molecular Biology, Umea University, 90187 Umea, Sweden"},{"name":"Department of Biomedical Sciences, Malmo University, 21428 Malmo, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M.","family":"Bonefeld","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8472-0771","authenticated-orcid":false,"given":"Carsten","family":"Geisler","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorbjorn","family":"Krejsgaard","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1153-8394","authenticated-orcid":false,"given":"Anja T.","family":"Fuglsang","sequence":"additional","affiliation":[{"name":"Department of Plant and Environmental Sciences, University of Copenhagen, 1871 Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-5624","authenticated-orcid":false,"given":"Niels","family":"Odum","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3008-735X","authenticated-orcid":false,"given":"Anders","family":"Woetmann","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/ajh.25577","article-title":"Mycosis fungoides and Sezary syndrome: 2019 update on diagnosis, risk-stratification, and management","volume":"94","author":"Hristov","year":"2019","journal-title":"Am. 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