{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sorger H"],"funding":["Austrian Science Fund FWF","European Association for Cancer Research","Medizinische Universität Graz"],"pagination":["e15200"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9727928"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(12)"],"pubmed_abstract":["Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell gro"],"journal":["EMBO molecular medicine"],"pubmed_title":["Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma."],"pmcid":["PMC9727928"],"funding_grant_id":["I 4218","741","W1241","SFB F04707‐B20","I 4157","SFB‐F06105"],"pubmed_authors":["Otte M","Dey S","Vieyra-Garcia PA","Spiegl B","de Araujo ED","Schlederer M","Pirker C","Cerroni L","Sedighi A","Albrecht JD","Nguyen VA","Braun T","Garces de Los Fayos Alonso I","Surbek M","Kenner L","Teufelberger AR","Poloske D","Timelthaler G","Heitzer E","Manaswiyoungkul P","Perchthaler I","Metzelder ML","Lazzeri I","Abdeldayem A","Graier T","Pan Y","Moriggl R","Fleck R","Wolf P","Fink-Puches R","Ober J","Merkel O","Gunning PT","Machtinger M","Andre F","Tin G","Olaoye OO","Orlova A","Kodajova P","Berger W","Wobser M","Nicolay JP","Herling M","Neubauer HA","Sorger H","Graf R"],"additional_accession":[]},"is_claimable":false,"name":"Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.","description":"Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell gro","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-13T16:02:27.51Z","creation":"2025-02-19T03:59:09.608Z"},"accession":"S-EPMC9727928","cross_references":{"pubmed":["36341492"],"doi":["10.15252/emmm.202115200"]}}