The Journal of Experimental Medicine
Rockland Immunochemicals for Research
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Published online February 25, 2008
doi:10.1084/jem.20072108
The Journal of Experimental Medicine, Vol. 205, No. 3, 585-594
The Rockefeller University Press, 0022-1007 $30.00
© 2008 O'Connell et al.
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ARTICLE

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

Ryan M. O'Connell1, Dinesh S. Rao1,2, Aadel A. Chaudhuri1, Mark P. Boldin1, Konstantin D. Taganov1, John Nicoll3, Ronald L. Paquette3, and David Baltimore1

1 Department of Biology, California Institute of Technology, Pasadena, CA 91125
2 Department of Pathology and Laboratory Medicine and 3 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095

CORRESPONDENCE David Baltimore: baltimo{at}caltech.edu

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.


Abbreviations used: AML, acute myeloid leukemia; FSC, forward scatter; GM, granulocyte/monocyte; HSC, hematopoietic stem cell; miRNA, microRNA; SSC, side scatter; UTR, untranslated region.


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