Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia
- Author
- Panagiotis Ntziachristos, Aristotelis Tsirigos, Pieter Van Vlierberghe (UGent) , Jelena Nedjic, Thomas Trimarchi, Maria Sol Flaherty, Dolors Ferres-Marco, Vanina da Ros, Zuojian Tang, Jasmin Siegle, Patrik Asp, Michael Hadler, Isaura Rigo, Kim De Keersmaecker, Jay Patel, Tien Huynh, Filippo Utro, Sandrine Poglio, Jeremy B Samon, Elisabeth Paietta, Janis Racevskis, Jacob M Rowe, Raul Rabadan, Ross L Levine, Stuart Brown, Françoise Pflumio, Maria Dominguez, Adolfo Ferrando and Iannis Aifantis
- Organization
- Abstract
- T cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling(1). 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.
- Keywords
- SOMATIC MUTATIONS, NOTCH1, GENOME, PRC2, EZH2, CONTEXT, H3
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-3126394
- MLA
- Ntziachristos, Panagiotis, et al. “Genetic Inactivation of the Polycomb Repressive Complex 2 in T Cell Acute Lymphoblastic Leukemia.” NATURE MEDICINE, vol. 18, no. 2, 2012, pp. 296–301, doi:10.1038/nm.2651.
- APA
- Ntziachristos, P., Tsirigos, A., Van Vlierberghe, P., Nedjic, J., Trimarchi, T., Flaherty, M. S., … Aifantis, I. (2012). Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. NATURE MEDICINE, 18(2), 296–301. https://doi.org/10.1038/nm.2651
- Chicago author-date
- Ntziachristos, Panagiotis, Aristotelis Tsirigos, Pieter Van Vlierberghe, Jelena Nedjic, Thomas Trimarchi, Maria Sol Flaherty, Dolors Ferres-Marco, et al. 2012. “Genetic Inactivation of the Polycomb Repressive Complex 2 in T Cell Acute Lymphoblastic Leukemia.” NATURE MEDICINE 18 (2): 296–301. https://doi.org/10.1038/nm.2651.
- Chicago author-date (all authors)
- Ntziachristos, Panagiotis, Aristotelis Tsirigos, Pieter Van Vlierberghe, Jelena Nedjic, Thomas Trimarchi, Maria Sol Flaherty, Dolors Ferres-Marco, Vanina da Ros, Zuojian Tang, Jasmin Siegle, Patrik Asp, Michael Hadler, Isaura Rigo, Kim De Keersmaecker, Jay Patel, Tien Huynh, Filippo Utro, Sandrine Poglio, Jeremy B Samon, Elisabeth Paietta, Janis Racevskis, Jacob M Rowe, Raul Rabadan, Ross L Levine, Stuart Brown, Françoise Pflumio, Maria Dominguez, Adolfo Ferrando, and Iannis Aifantis. 2012. “Genetic Inactivation of the Polycomb Repressive Complex 2 in T Cell Acute Lymphoblastic Leukemia.” NATURE MEDICINE 18 (2): 296–301. doi:10.1038/nm.2651.
- Vancouver
- 1.Ntziachristos P, Tsirigos A, Van Vlierberghe P, Nedjic J, Trimarchi T, Flaherty MS, et al. Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. NATURE MEDICINE. 2012;18(2):296–301.
- IEEE
- [1]P. Ntziachristos et al., “Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia,” NATURE MEDICINE, vol. 18, no. 2, pp. 296–301, 2012.
@article{3126394,
abstract = {{T cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling(1). 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.}},
author = {{Ntziachristos, Panagiotis and Tsirigos, Aristotelis and Van Vlierberghe, Pieter and Nedjic, Jelena and Trimarchi, Thomas and Flaherty, Maria Sol and Ferres-Marco, Dolors and da Ros, Vanina and Tang, Zuojian and Siegle, Jasmin and Asp, Patrik and Hadler, Michael and Rigo, Isaura and De Keersmaecker, Kim and Patel, Jay and Huynh, Tien and Utro, Filippo and Poglio, Sandrine and Samon, Jeremy B and Paietta, Elisabeth and Racevskis, Janis and Rowe, Jacob M and Rabadan, Raul and Levine, Ross L and Brown, Stuart and Pflumio, Françoise and Dominguez, Maria and Ferrando, Adolfo and Aifantis, Iannis}},
issn = {{1078-8956}},
journal = {{NATURE MEDICINE}},
keywords = {{SOMATIC MUTATIONS,NOTCH1,GENOME,PRC2,EZH2,CONTEXT,H3}},
language = {{eng}},
number = {{2}},
pages = {{296--301}},
title = {{Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia}},
url = {{http://doi.org/10.1038/nm.2651}},
volume = {{18}},
year = {{2012}},
}
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