{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:57:47Z","timestamp":1772755067992,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University","award":["RM11715C7C626BAB"],"award-info":[{"award-number":["RM11715C7C626BAB"]}]},{"name":"Sapienza University","award":["RM12117A71419448"],"award-info":[{"award-number":["RM12117A71419448"]}]},{"name":"Sapienza University","award":["L. 232\/2016"],"award-info":[{"award-number":["L. 232\/2016"]}]},{"name":"Italian Ministry of Education, University, and Research\u2014Dipartimenti di Eccellenza","award":["RM11715C7C626BAB"],"award-info":[{"award-number":["RM11715C7C626BAB"]}]},{"name":"Italian Ministry of Education, University, and Research\u2014Dipartimenti di Eccellenza","award":["RM12117A71419448"],"award-info":[{"award-number":["RM12117A71419448"]}]},{"name":"Italian Ministry of Education, University, and Research\u2014Dipartimenti di Eccellenza","award":["L. 232\/2016"],"award-info":[{"award-number":["L. 232\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>T-cell acute lymphoblastic leukemia is an aggressive neoplasia due to hyper-proliferation of lymphoid progenitors and lacking a definitive cure to date. Notch-activating mutations are the most common in driving disease onset and progression, often in combination with sustained activity of NF-\u03baB. Myeloid-derived suppressor cells represent a mixed population of immature progenitors exerting suppression of anti-cancer immune responses in the tumor microenvironment of many malignancies. We recently reported that in a transgenic murine model of Notch3-dependent T-cell acute lymphoblastic leukemia there is an accumulation of myeloid-derived suppressor cells, dependent on both Notch signaling deregulation and IL-6 production inside tumor T-cells. However, possible interaction between NF-\u03baB and Notch in this context remains unexplored. Interestingly, we also reported that Notch3 transgenic and NF-\u03baB1\/p50 deleted double mutant mice display massive myeloproliferation. Here, we demonstrated that the absence of the p50 subunit in these mice dramatically enhances the induction and suppressive function of myeloid-derived suppressor cells. This runs in parallel with an impressive increase in IL-6 concentration in the peripheral blood serum, depending on IL-6 hyper-production by tumor T-cells from double mutant mice. Mechanistically, IL-6 increase relies on loss of the negative control exerted by the p50 subunit on the IL-6 promoter. Our results reveal the Notch\/NF-\u03baB cross-talk in regulating myeloid-derived suppressor cell biology in T-cell leukemia, highlighting the need to consider carefully the pleiotropic effects of NF-\u03baB-based therapy on the tumor microenvironment.<\/jats:p>","DOI":"10.3390\/ijms25189882","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T03:03:37Z","timestamp":1726196617000},"page":"9882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The NF-\u03baB1\/p50 Subunit Influences the Notch\/IL-6-Driven Expansion of Myeloid-Derived Suppressor Cells in Murine T-Cell Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"25","author":[{"given":"Behnaz","family":"Abdollahzadeh","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noemi Martina","family":"Cantale Aeo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nike","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Orlando","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7882-8787","authenticated-orcid":false,"given":"Maria","family":"Basciani","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6517-9107","authenticated-orcid":false,"given":"Giovanna","family":"Peruzzi","sequence":"additional","affiliation":[{"name":"Center for Life Nano- and Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Grazioli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Screpanti","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-2611","authenticated-orcid":false,"given":"Maria Pia","family":"Felli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Francesco","family":"Campese","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shiraz, P., Jehangir, W., and Agrawal, V. 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