TY - JOUR
T1 - Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
AU - O'Connell, Ryan M.
AU - Rao, Dinesh S.
AU - Chaudhuri, Aadel A.
AU - Boldin, Mark P.
AU - Taganov, Konstantin D.
AU - Nicoll, John
AU - Paquette, Ronald L.
AU - Baltimore, David
PY - 2008/3/17
Y1 - 2008/3/17
N2 - 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-55 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. JEM
AB - 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-55 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. JEM
UR - http://www.scopus.com/inward/record.url?scp=41149130219&partnerID=8YFLogxK
U2 - 10.1084/jem.20072108
DO - 10.1084/jem.20072108
M3 - Article
C2 - 18299402
AN - SCOPUS:41149130219
SN - 0022-1007
VL - 205
SP - 585
EP - 594
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -