{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T11:40:47Z","timestamp":1697283647751},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,7,12]],"date-time":"2006-07-12T00:00:00Z","timestamp":1152662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dysregulated Notch signaling accounts for the majority of acute T lymphoblastic leukemia\/lymphoma (T\u2010ALL) cases in humans. Here, we characterize lymphomas from Notch1IC transgenic rats, which develop T\u2010ALL shortly after weaning, and show that they display a number of previously undocumented features. Starting from monoclonal thymic tumors, the CD4<jats:sup>+<\/jats:sup>CD8\u03b1\u03b1<jats:sup>+<\/jats:sup> lymphoma cells infiltrate the bone marrow and then spread to secondary lymphoid and non\u2010lymphoid organs. However, major hallmarks of T\u2010ALL cells in other murine models and human patients, such as constitutive NF\u2010\u03baB activity and increased levels of anti\u2010apoptotic proteins, are remarkably absent in Notch1IC lymphomas. In contrast, CD30, a classic marker of Hodgkin lymphomas, is overexpressed in these tumors. Intriguingly, enforced Notch1 signaling up\u2010regulates expression of Notch3, which has also been implicated in the pathogenesis of T\u2010ALL. By blocking endogenous Notch signaling, we could demonstrate that Notch1IC is sufficient to induce sustained preTCR expression in transgenic thymocytes but not for their progression to the double\u2010positive stage. This suggests that other Notch activities may also contribute to the phenotype of the transgenic rats. In summary, we anticipate this new animal model will help to further elucidate the role of Notch1 in the pathogenesis of T\u2010ALL.<\/jats:p>","DOI":"10.1002\/eji.200535791","type":"journal-article","created":{"date-parts":[[2006,7,12]],"date-time":"2006-07-12T17:41:11Z","timestamp":1152726071000},"page":"2223-2234","source":"Crossref","is-referenced-by-count":7,"title":["Unexpected features of acute T lymphoblastic lymphomas in Notch1IC transgenic rats"],"prefix":"10.1002","volume":"36","author":[{"given":"Jens","family":"van den 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