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

Ryan M. O'Connell, Dinesh S. Rao, Aadel A. Chaudhuri, Mark P. Boldin, Konstantin D. Taganov, John Nicoll, Ronald L. Paquette, David Baltimore

Research output: Contribution to journalArticlepeer-review

579 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)585-594
Number of pages10
JournalJournal of Experimental Medicine
Volume205
Issue number3
DOIs
StatePublished - Mar 17 2008

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