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These GATA-3 dependent transcriptional programs, in collaboration with the genetic landscape, promote cell growth and survival, and confer resistance to conventional chemotherapeutic agents. We observed that transcriptional cyclin dependent kinase 9 (CDK9) activation regulates diverse oncogenic transcriptional programs in these aggressive T-cell lymphomas and is thus a novel therapeutic vulnerability. Using complementary and orthogonal approaches, we identified multiple independent mechanisms by which CDK9 promotes T-cell lymphomagenesis, including a mechanism by which GATA-3 promotes CDK9 activation at GATA-3 dependent loci. We also identify novel mechanisms by which GATA-3 and CDK9 regulate rRNA transcription and processing, respectively, collaboratively promoting ribosome biogenesis. Therefore, CDK9 is a therapeutic vulnerability across genetically and transcriptionally diverse T-cell lymphomas, including those for which GATA-3 is oncogenic.<\/jats:p>","DOI":"10.1038\/s41408-025-01427-1","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:46:42Z","timestamp":1764262002000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CDK9 is a dependency in GATA-3 driven and MCL-1 independent T-cell Lymphomas"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9082-2117","authenticated-orcid":false,"given":"Chenguang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhaib","family":"Abdelrahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0682-5236","authenticated-orcid":false,"given":"Xiangrong","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Burgess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying S.","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Ahmar","family":"Rauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nermin","family":"Kady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara A.","family":"Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira P.","family":"Maine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Boonstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9457-7587","authenticated-orcid":false,"given":"Kirill","family":"Sabitov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2238-5066","authenticated-orcid":false,"given":"Carlos","family":"Murga-Zamalloa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6420-0760","authenticated-orcid":false,"given":"Ryan A.","family":"Wilcox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"1427_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1101441","volume":"13","author":"J Weiss","year":"2023","unstructured":"Weiss J, Reneau J, Wilcox RA. 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