Academic Journal
A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia.
| العنوان: | A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. |
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| المؤلفون: | Herranz, Daniel, Ambesi-Impiombato, Alberto, Palomero, Teresa, Schnell, Stephanie A, Belver, Laura, Wendorff, Agnieszka A, Xu, Luyao, Castillo-Martin, Mireia, Llobet-Navás, David, Cordon-Cardo, Carlos, Clappier, Emmanuelle, Soulier, Jean, Ferrando, Adolfo A |
| المصدر: | Nat Med ; ISSN:1546-170X ; Volume:20 ; Issue:10 |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2014 |
| المجموعة: | PubMed Central (PMC) |
| الوصف: | Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by recurrent chromosomal duplications in human T cell acute lymphoblastic leukemia (T-ALL). This highly conserved regulatory element, hereby named N-Me for NOTCH MYC enhancer, is located within a broad super-enhancer region +1.47 Mb from the MYC transcription initiating site, interacts with the MYC proximal promoter and induces orientation-independent MYC expression in reporter assays. Moreover, analysis of N-Me knockout mice demonstrates a selective and essential role of this regulatory element during thymocyte development and in NOTCH1-induced T-ALL. Together these results identify N-Me as a long-range oncogenic enhancer implicated directly in the pathogenesis of human leukemia and highlight the importance of the NOTCH1-MYC regulatory axis in T cell transformation and as a therapeutic target in T-ALL. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://doi.org/10.1038/nm.3665; https://pubmed.ncbi.nlm.nih.gov/25194570; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192073/ |
| DOI: | 10.1038/nm.3665 |
| الاتاحة: | https://doi.org/10.1038/nm.3665 https://pubmed.ncbi.nlm.nih.gov/25194570 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192073/ |
| رقم الانضمام: | edsbas.51A83771 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/nm.3665 |
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