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A novel tumor suppressor function for the Notch pathway in myeloid leukemia
Notch signaling is a central regulator of differentiation in a variety of organisms and tissue types(1). Its activity is controlled by the multi-subunit γ–secretase complex (γSE) complex(2). Although Notch signaling can play both oncogenic and tumor suppressor roles in solid tumors, in the hematopoi...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093658/ https://www.ncbi.nlm.nih.gov/pubmed/21562564 http://dx.doi.org/10.1038/nature09999 |
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author | Klinakis, Apostolos Lobry, Camille Abdel-Wahab, Omar Oh, Philmo Haeno, Hiroshi Buonamici, Silvia van De Walle, Inge Cathelin, Severine Trimarchi, Thomas Araldi, Elisa Liu, Cynthia Ibrahim, Sherif Beran, Miroslav Zavadil, Jiri Efstratiadis, Argiris Taghon, Tom Michor, Franziska Levine, Ross L. Aifantis, Iannis |
author_facet | Klinakis, Apostolos Lobry, Camille Abdel-Wahab, Omar Oh, Philmo Haeno, Hiroshi Buonamici, Silvia van De Walle, Inge Cathelin, Severine Trimarchi, Thomas Araldi, Elisa Liu, Cynthia Ibrahim, Sherif Beran, Miroslav Zavadil, Jiri Efstratiadis, Argiris Taghon, Tom Michor, Franziska Levine, Ross L. Aifantis, Iannis |
author_sort | Klinakis, Apostolos |
collection | PubMed |
description | Notch signaling is a central regulator of differentiation in a variety of organisms and tissue types(1). Its activity is controlled by the multi-subunit γ–secretase complex (γSE) complex(2). Although Notch signaling can play both oncogenic and tumor suppressor roles in solid tumors, in the hematopoietic system, it is exclusively oncogenic, notably in T cell acute lymphoblastic leukemia (T-ALL), a disease characterized by Notch1 activating mutations(3). Here we identify novel somatic inactivating Notch pathway mutations in a fraction of chronic myelomonocytic leukemia (CMML) patients. Inactivation of Notch signaling in mouse hematopoietic stem cells (HSC) resulted in an aberrant accumulation of granulocyte/monocyte progenitors (GMP), extramedullary hematopoieisis and the induction of CMML-like disease. Transcriptome analysis revealed that Notch signaling regulates an extensive myelomonocytic-specific gene signature, through the direct suppression of gene transcription by the Notch target Hes1. Our studies identify a novel role for Notch signaling during early hematopoietic stem cell differentiation and suggest that the Notch pathway can play both tumor-promoting and suppressive roles within the same tissue. |
format | Text |
id | pubmed-3093658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
spelling | pubmed-30936582011-11-12 A novel tumor suppressor function for the Notch pathway in myeloid leukemia Klinakis, Apostolos Lobry, Camille Abdel-Wahab, Omar Oh, Philmo Haeno, Hiroshi Buonamici, Silvia van De Walle, Inge Cathelin, Severine Trimarchi, Thomas Araldi, Elisa Liu, Cynthia Ibrahim, Sherif Beran, Miroslav Zavadil, Jiri Efstratiadis, Argiris Taghon, Tom Michor, Franziska Levine, Ross L. Aifantis, Iannis Nature Article Notch signaling is a central regulator of differentiation in a variety of organisms and tissue types(1). Its activity is controlled by the multi-subunit γ–secretase complex (γSE) complex(2). Although Notch signaling can play both oncogenic and tumor suppressor roles in solid tumors, in the hematopoietic system, it is exclusively oncogenic, notably in T cell acute lymphoblastic leukemia (T-ALL), a disease characterized by Notch1 activating mutations(3). Here we identify novel somatic inactivating Notch pathway mutations in a fraction of chronic myelomonocytic leukemia (CMML) patients. Inactivation of Notch signaling in mouse hematopoietic stem cells (HSC) resulted in an aberrant accumulation of granulocyte/monocyte progenitors (GMP), extramedullary hematopoieisis and the induction of CMML-like disease. Transcriptome analysis revealed that Notch signaling regulates an extensive myelomonocytic-specific gene signature, through the direct suppression of gene transcription by the Notch target Hes1. Our studies identify a novel role for Notch signaling during early hematopoietic stem cell differentiation and suggest that the Notch pathway can play both tumor-promoting and suppressive roles within the same tissue. 2011-05-12 /pmc/articles/PMC3093658/ /pubmed/21562564 http://dx.doi.org/10.1038/nature09999 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Klinakis, Apostolos Lobry, Camille Abdel-Wahab, Omar Oh, Philmo Haeno, Hiroshi Buonamici, Silvia van De Walle, Inge Cathelin, Severine Trimarchi, Thomas Araldi, Elisa Liu, Cynthia Ibrahim, Sherif Beran, Miroslav Zavadil, Jiri Efstratiadis, Argiris Taghon, Tom Michor, Franziska Levine, Ross L. Aifantis, Iannis A novel tumor suppressor function for the Notch pathway in myeloid leukemia |
title | A novel tumor suppressor function for the Notch pathway in myeloid leukemia |
title_full | A novel tumor suppressor function for the Notch pathway in myeloid leukemia |
title_fullStr | A novel tumor suppressor function for the Notch pathway in myeloid leukemia |
title_full_unstemmed | A novel tumor suppressor function for the Notch pathway in myeloid leukemia |
title_short | A novel tumor suppressor function for the Notch pathway in myeloid leukemia |
title_sort | novel tumor suppressor function for the notch pathway in myeloid leukemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093658/ https://www.ncbi.nlm.nih.gov/pubmed/21562564 http://dx.doi.org/10.1038/nature09999 |
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