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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Bibliographic Details
Published in:The Journal of experimental medicine 2008-03, Vol.205 (3), p.585-594
Main Authors: O'Connell, Ryan M, Rao, Dinesh S, Chaudhuri, Aadel A, Boldin, Mark P, Taganov, Konstantin D, Nicoll, John, Paquette, Ronald L, Baltimore, David
Format: Article
Language:English
Subjects:
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Animals
Female
Gene Expression - drug effects
Granulocytes - immunology
Granulocytes - metabolism
Granulocytes - pathology
Hematopoiesis - genetics
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - immunology
Hematopoietic Stem Cells - metabolism
Hematopoietic Stem Cells - pathology
Humans
Immunity, Innate
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - metabolism
Lipopolysaccharides - toxicity
Mice
Mice, Inbred C57BL
MicroRNAs - genetics
MicroRNAs - metabolism
Monocytes - immunology
Monocytes - metabolism
Monocytes - pathology
Myeloproliferative Disorders - etiology
Myeloproliferative Disorders - genetics
Myeloproliferative Disorders - metabolism
Myeloproliferative Disorders - pathology
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Summary: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.
ISSN:0022-1007
1540-9538
1892-1007
DOI:10.1084/jem.20072108