{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:15:40Z","timestamp":1790964940113,"version":"4.1.0"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,3,19]]},"abstract":"<jats:p>Notch receptors are conserved regulators of cell fate and have been implicated in the regulation of T cell differentiation and lymphomagenesis. However, neither the generality of Notch involvement in leukemia, nor the molecules with which Notch may interact have been clarified. Recently, we showed that transgenic mice expressing the constitutively active intracellular domain of Notch3 in thymocytes and T cells developed early and aggressive T cell neoplasias. Although primarily splenic, the tumors sustained features of immature thymocytes, including expression of pT\u03b1, a defining component of the pre T cell receptor, known to be a potent signaling complex provoking thymocyte survival, proliferation, and activation. Thus, enforced expression of Notch3, which is ordinarily down-regulated as thymocytes mature, may sustain pre T cell receptor expression, causing dysregulated hyperplasia. This hypothesis has been successfully tested in this article by the observation that deletion of pT\u03b1 in Notch3 transgenic mice abrogates tumor development, indicating a crucial role for pT\u03b1 in T cell leukemogenesis. Parallel observations were made in humans, in that all T cell acute lymphoblastic leukemias examined showed expression of Notch3 and of the Notch target gene HES-1, as well as of pT\u03b1 a and b transcripts, whereas the expression of all these genes was dramatically reduced or absent in remission. Together, these results suggest that the combined expression of Notch3 and pT\u03b1 sustains T cell leukemogenesis and may represent pathognomonic molecular features of human T-ALL.<\/jats:p>","DOI":"10.1073\/pnas.062050599","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"3788-3793","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":179,"title":["Combined expression of pT\u03b1 and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis"],"prefix":"10.1073","volume":"99","author":[{"given":"Diana","family":"Bellavia","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio F.","family":"Campese","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saula","family":"Checquolo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Balestri","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cazzaniga","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urban","family":"Lendahl","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Fehling","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian C.","family":"Hayday","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Frati","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"von Boehmer","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Gulino","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Screpanti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University \u201cLa Sapienza,\u201d Viale Regina Elena 324, 00161 Roma, Italy; Department of Experimental Medicine, University of L'Aquila, Via Vetoio-Coppito, 2-67100 L'Aquila, Italy; Tettamanti Research Center, New S. Gerardo's Hospital, University of Milano-Bicocca, 20052 Monza, Italy; Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; Department of Immunology, Medical Faculty\/University Clinics, D-89070 Ulm,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,3,12]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.2.343.343"},{"key":"e_1_3_3_2_2","first-page":"55","volume":"220","author":"Baer R","year":"1997","unstructured":"R Baer, L-Y Hwang, R O Bash Curr Top Microbiol Immunol 220, 55\u201365 (1997).","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90111-B"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(00)01828-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2283"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.11.8071-8080.1996"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.13.3337"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4049\/jimmunol.161.1.11","volume":"161","author":"Barber D F","year":"1998","unstructured":"D F Barber, L Passoni, L Wen, L Geng, A C Hayday J Immunol 161, 11\u201316 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/11.7.1017"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.433"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/375795a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950200603"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716513"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.12.7166"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.9.1203"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.9.5106"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.7.F43"},{"key":"e_1_3_3_19_2","first-page":"90","volume":"189","author":"Rothenberg E V","year":"2001","unstructured":"E V Rothenberg Nat Immunol 189, 90\u201392 (2001).","journal-title":"Nat Immunol"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00901-1"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.20.7505-7515.2000"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00009-1"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/77819"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.7.979"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.4.2157"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.4.2230"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.12b.2620"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.6.733"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.2.429-440.2000"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.1.99"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/35020093"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.062050599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T08:19:36Z","timestamp":1682151576000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.062050599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,3,12]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2002,3,19]]}},"alternative-id":["10.1073\/pnas.062050599"],"URL":"https:\/\/doi.org\/10.1073\/pnas.062050599","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,3,12]]},"assertion":[{"value":"2001-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-01-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-03-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}