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Título: | Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia |
Autor: | Ferres-Marco, Dolores CSIC ORCID; Ros, Vanina da CSIC ORCID; Domínguez, María CSIC ORCID | Fecha de publicación: | 2012 | Editor: | Nature Publishing Group | Citación: | Nature Medicine 18(2): 296- 301 (2012) | Resumen: | T cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling1. In this study we report the presence of loss-of-function mutations and deletions of the EZH2 and SUZ12 genes, which encode crucial components of the Polycomb repressive complex 2 (PRC2) 2,3, in 25% of T-ALLs. To further study the role of PRC2 in T-ALL, we used NOTCH1-dependent mouse models of the disease, as well as human T-ALL samples, and combined locus-specific and global analysis of NOTCH1-driven epigenetic changes. These studies demonstrated that activation of NOTCH1 specifically induces loss of the repressive mark Lys27 trimethylation of histone 3 (H3K27me3) 4 by antagonizing the activity of PRC2. These studies suggest a tumor suppressor role for PRC2 in human leukemia and suggest a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gene expression and cell transformation. © 2012 Nature America, Inc. All rights reserved. | URI: | http://hdl.handle.net/10261/66875 | DOI: | 10.1038/nm.2651 | Identificadores: | doi: 10.1038/nm.2651 issn: 1078-8956 e-issn: 1546-170X |
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