{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T15:41:13Z","timestamp":1775662873202,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Drs. Martin &amp; Dorothy Spatz Foundation","award":["P30CA16672"],"award-info":[{"award-number":["P30CA16672"]}]},{"name":"University of Texas MD Anderson Cancer Center Institutional Research Grant","award":["P30CA16672"],"award-info":[{"award-number":["P30CA16672"]}]},{"name":"Fred Pearce Fund for CTCL Research","award":["P30CA16672"],"award-info":[{"award-number":["P30CA16672"]}]},{"name":"MD Anderson Cancer Center Support Grant","award":["P30CA16672"],"award-info":[{"award-number":["P30CA16672"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a JAK3 mutation was reported in a small portion of CTCL patients. In this study, we assessed the oncogenic roles of a newly identified JAK3-INSL3 fusion transcript in CTCL. Total RNA from malignant T-cells in 33 patients with S\u00e9zary syndrome (SS), a leukemic form of CTCL, was examined for the new JAK3-INSL3 fusion transcript by RT-PCR followed by Sanger sequencing. The expression levels were assessed by qPCR and correlated with patient survivals. Knockdown and\/or knockout assays were conducted in two CTCL cell lines (MJ cells and HH cells) by RNA interference and\/or CRISPR\/Cas9 gene editing. SS patients expressed heterogeneous levels of a new JAK3-INSL3 fusion transcript. Patients with high-level expression of JAK3-INSL3 showed poorer 5-year survival (n = 19, 42.1%) than patients with low-level expression (n = 14, 78.6%). CTCL cells transduced with specific shRNAs or sgRNAs had decreased new JAK3-INSL3 fusion transcript expression, reduced cell proliferation, and decreased colony formation. In NSG xenograft mice, smaller tumor sizes were observed in MJ cells transduced with specific shRNAs than cells transduced with controls. Our results suggest that the newly identified JAK3-INSL3 fusion transcript confers an oncogenic event in CTCL.<\/jats:p>","DOI":"10.3390\/cells12192381","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T05:48:13Z","timestamp":1695966493000},"page":"2381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["New JAK3-INSL3 Fusion Transcript\u2014An Oncogenic Event in Cutaneous T-Cell Lymphoma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1451-6879","authenticated-orcid":false,"given":"Loka Reddy","family":"Velatooru","sequence":"first","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng Hui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedram","family":"Bijani","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierr","family":"Bojaxhi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-7405","authenticated-orcid":false,"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeleine","family":"Duvic","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-446X","authenticated-orcid":false,"given":"Xiao","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1182\/blood-2007-03-055749","article-title":"Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","volume":"110","author":"Olsen","year":"2007","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.12688\/f1000research.8829.1","article-title":"An overview of cutaneous T cell lymphomas","volume":"5","author":"Bagherani","year":"2016","journal-title":"F1000Research"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1309\/U1Y6-J4AG-5M4M-7AYV","article-title":"Absence of CD26 expression is a useful marker for diagnosis of T-cell lymphoma in peripheral blood","volume":"115","author":"Jones","year":"2001","journal-title":"Am. 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