Academic Journal
Intrathymic Notch3 and CXCR4 combinatorial interplay facilitates T-cell leukemia propagation.
| العنوان: | Intrathymic Notch3 and CXCR4 combinatorial interplay facilitates T-cell leukemia propagation. |
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| المؤلفون: | ferrandino, francesca, BERNARDINI, Giovanni, TSAOULI, GEORGIA, Grazioli Paola, Campese Antonio Francesco, Noce Claudia, Ciuffetta Ambra, Vacca Alessandra, Besharat Zein Mersini, Bellavia Diana, SCREPANTI, Isabella, Felli Maria Pia |
| المساهمون: | Ferrandino, Francesca, Bernardini, Giovanni, Tsaouli, Georgia, Grazioli, Paola, Campese, Antonio Francesco, Noce, Claudia, Ciuffetta, Ambra, Vacca, Alessandra, Besharat, ZEIN MERSINI, Bellavia, Diana, Screpanti, Isabella, Felli, MARIA PIA |
| بيانات النشر: | Macmillan |
| سنة النشر: | 2018 |
| المجموعة: | Sapienza Università di Roma: CINECA IRIS |
| مصطلحات موضوعية: | Notch3, CXCR4, Thymocytes, T-cell migration, beta-arrestin1, T-cell Leukemia |
| الوصف: | Notch hyperactivation dominates T-cell acute lymphoblastic leukemia development, but the mechanisms underlying "pre-leukemic-cells" dissemination are still unclear. Here we describe how deregulated Notch3 signaling enhances CXCR4 cell-surface expression and migratory ability of CD4+CD8+ thymocytes, possibly contributing to “pre-leukemic” cell propagation, early in disease progression. In transgenic mice overexpressing the constitutively active Notch3 intracellular domain, we detect the progressive increase in circulating blood and bone marrow of CD4+CD8+-cells, characterized by high and combined surface expression of Notch3 and CXCR4. We report for the first time that transplantation of such CD4+CD8+-cells, reveals their competence in infiltrating spleen and bone marrow of immunocompromised recipient mice. We also show that CXCR4 surface expression is central to the migratory ability of CD4+CD8+-cells and that such an expression is regulated by Notch3 through -arrestin in human leukemia cells. De novo, we propose that hyperactive Notch3 signaling by boosting CXCR4-dependent migration promotes anomalous egression of CD4+CD8+-cells from the thymus in early leukemia stages. In fact, in vivo CXCR4 antagonism prevents bone marrow colonization by such CD4+CD8+ cells in young Notch3 transgenic mice. Therefore, our data suggest that combined therapies precociously counteracting intrathymic Notch3/CXCR4 crosstalk, may prevent dissemination of “pre-leukemic” CD4+CD8+-cells, by a “thymus-autonomous” mechanism. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/30038265; info:eu-repo/semantics/altIdentifier/wos/WOS:000452384400001; journal:ONCOGENE; http://hdl.handle.net/11573/1119498; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85050377995 |
| DOI: | 10.1038/s41388-018-0401-2 |
| الاتاحة: | http://hdl.handle.net/11573/1119498 https://doi.org/10.1038/s41388-018-0401-2 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.91A8ED18 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41388-018-0401-2 |
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