{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:18:48Z","timestamp":1785323928236,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Amy Stelzer Manasevit Research Program","award":["MFAG 22889"],"award-info":[{"award-number":["MFAG 22889"]}]},{"name":"Amy Stelzer Manasevit Research Program","award":["RP12117A63FBA27C"],"award-info":[{"award-number":["RP12117A63FBA27C"]}]},{"name":"Amy Stelzer Manasevit Research Program","award":["RP122181642E92CE"],"award-info":[{"award-number":["RP122181642E92CE"]}]},{"name":"Italian Association for Cancer Research","award":["MFAG 22889"],"award-info":[{"award-number":["MFAG 22889"]}]},{"name":"Italian Association for Cancer Research","award":["RP12117A63FBA27C"],"award-info":[{"award-number":["RP12117A63FBA27C"]}]},{"name":"Italian Association for Cancer Research","award":["RP122181642E92CE"],"award-info":[{"award-number":["RP122181642E92CE"]}]},{"name":"Ministero Della Salute","award":["MFAG 22889"],"award-info":[{"award-number":["MFAG 22889"]}]},{"name":"Ministero Della Salute","award":["RP12117A63FBA27C"],"award-info":[{"award-number":["RP12117A63FBA27C"]}]},{"name":"Ministero Della Salute","award":["RP122181642E92CE"],"award-info":[{"award-number":["RP122181642E92CE"]}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University","doi-asserted-by":"publisher","award":["MFAG 22889"],"award-info":[{"award-number":["MFAG 22889"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University","doi-asserted-by":"publisher","award":["RP12117A63FBA27C"],"award-info":[{"award-number":["RP12117A63FBA27C"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University","doi-asserted-by":"publisher","award":["RP122181642E92CE"],"award-info":[{"award-number":["RP122181642E92CE"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>T-cell acute lymphoblastic leukemia (T-ALL) is a hematological cancer characterized by the infiltration of immature T-cells in the bone marrow. Aberrant NOTCH signaling in T-ALL is mainly triggered by activating mutations of NOTCH1 and overexpression of NOTCH3, and rarely is it linked to NOTCH3-activating mutations. Besides the known critical role of NOTCH, the nature of intrathymic microenvironment-dependent mechanisms able to render immature thymocytes, presumably pre-leukemic cells, capable of escaping thymus retention and infiltrating the bone marrow is still unclear. An important challenge is understanding how leukemic cells shape their tumor microenvironment to increase their ability to infiltrate and survive within. Our previous data indicated that hyperactive NOTCH3 affects the CXCL12\/CXCR4 system and may interfere with T-cell\/stroma interactions within the thymus. This study aims to identify the biological effects of the reciprocal interactions between human leukemic cell lines and thymic epithelial cell (TEC)-derived soluble factors in modulating NOTCH signaling and survival programs of T-ALL cells and TECs. The overarching hypothesis is that this crosstalk can influence the progressive stages of T-cell development driving T-cell leukemia. Thus, we investigated the effect of extracellular space conditioned by T-ALL cell lines (Jurkat, TALL1, and Loucy) and TECs and studied their reciprocal regulation of cell cycle and survival. In support, we also detected metabolic changes as potential drivers of leukemic cell survival. Our studies could shed light on T-cell\/stroma crosstalk to human leukemic cells and propose our culture system to test pharmacological treatment for T-ALL.<\/jats:p>","DOI":"10.3390\/ijms25031412","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T04:35:40Z","timestamp":1706070940000},"page":"1412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Thymic-Epithelial-Cell-Dependent Microenvironment Influences Proliferation and Apoptosis of Leukemic Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-1007","authenticated-orcid":false,"given":"Sandesh Kumar","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezda","family":"Zhdanovskaya","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Sergio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Cardinale","sequence":"additional","affiliation":[{"name":"Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6012-414X","authenticated-orcid":false,"given":"Marco","family":"Rosichini","sequence":"additional","affiliation":[{"name":"Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Varricchio","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Pace","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-6782","authenticated-orcid":false,"given":"Carlo","family":"Capalbo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7976-3654","authenticated-orcid":false,"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Catholic University of the Sacred Heart, 12631 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-1400","authenticated-orcid":false,"given":"Alberto","family":"Macone","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8383-0453","authenticated-orcid":false,"given":"Enrico","family":"Velardi","sequence":"additional","affiliation":[{"name":"Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Palermo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1182\/blood-2003-09-3243","article-title":"Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival","volume":"103","author":"Chiaretti","year":"2004","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shiraz, P., Jehangir, W., and Agrawal, V. 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