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Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder

Mammalian microRNAs are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonst...

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Autores principales: O'Connell, Ryan M., Rao, Dinesh S., Chaudhuri, Aadel A., Boldin, Mark P., Taganov, Konstantin D., Nicoll, John, Paquette, Ronald L., Baltimore, David
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275382/
https://www.ncbi.nlm.nih.gov/pubmed/18299402
http://dx.doi.org/10.1084/jem.20072108
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author O'Connell, Ryan M.
Rao, Dinesh S.
Chaudhuri, Aadel A.
Boldin, Mark P.
Taganov, Konstantin D.
Nicoll, John
Paquette, Ronald L.
Baltimore, David
author_facet O'Connell, Ryan M.
Rao, Dinesh S.
Chaudhuri, Aadel A.
Boldin, Mark P.
Taganov, Konstantin D.
Nicoll, John
Paquette, Ronald L.
Baltimore, David
author_sort O'Connell, Ryan M.
collection PubMed
description Mammalian microRNAs are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the miR-155–induced GM populations displayed pathological features characteristic of myeloid neoplasia. Of possible relevance to human disease, miR-155 was found to be overexpressed in the bone marrow of patients with certain subtypes of acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress.
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spelling pubmed-22753822008-09-17 Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder O'Connell, Ryan M. Rao, Dinesh S. Chaudhuri, Aadel A. Boldin, Mark P. Taganov, Konstantin D. Nicoll, John Paquette, Ronald L. Baltimore, David J Exp Med Articles Mammalian microRNAs are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the miR-155–induced GM populations displayed pathological features characteristic of myeloid neoplasia. Of possible relevance to human disease, miR-155 was found to be overexpressed in the bone marrow of patients with certain subtypes of acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress. The Rockefeller University Press 2008-03-17 /pmc/articles/PMC2275382/ /pubmed/18299402 http://dx.doi.org/10.1084/jem.20072108 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
O'Connell, Ryan M.
Rao, Dinesh S.
Chaudhuri, Aadel A.
Boldin, Mark P.
Taganov, Konstantin D.
Nicoll, John
Paquette, Ronald L.
Baltimore, David
Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
title Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
title_full Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
title_fullStr Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
title_full_unstemmed Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
title_short Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
title_sort sustained expression of microrna-155 in hematopoietic stem cells causes a myeloproliferative disorder
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275382/
https://www.ncbi.nlm.nih.gov/pubmed/18299402
http://dx.doi.org/10.1084/jem.20072108
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