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

作者：Ryan M. O’Connell, Dinesh S. Rao, Aadel A. Chaudhuri, Mark Boldin, Konstantin D. Taganov, John M. Nicoll, RONALD L. PAQUETTE, David Baltimore · 发表于：The Journal of Experimental Medicine · 年份：2008 · DOI：10.1084/jem.20072108 · 被引用次数：687 · 研究领域：MicroRNA in disease regulation、Extracellular vesicles in disease、RNA Interference and Gene Delivery

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.