Narayan, N.Morenos, L.Phipson, B.Willis, S.Brumatti, G.Eggers, S.Lalaoui, N.Brown, L.Kosasih, H.Bartolo, R.Zhou, L.Catchpoole, D.Saffery, R.Oshlack, A.Goodall, G.Ekert, P.2019-03-172019-03-172017Leukemia, 2017; 31(4):808-8200887-69241476-5551http://hdl.handle.net/2440/118197Enforced expression of microRNA-155 (miR-155) in myeloid cells has been shown to have both oncogenic or tumour-suppressor functions in acute myeloid leukaemia (AML). We sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human paediatric AML data sets. We show that the highest miR-155 expression levels inhibited proliferation in murine AML models. Over time, enforced miR-155 expression in AML in vitro and in vivo, however, favours selection of intermediate miR-155 expression levels that results in increased tumour burden in mice, without accelerating the onset of disease. Strikingly, we show that intermediate and high miR-155 expression also regulate very different subsets of miR-155 targets and have contrasting downstream effects on the transcriptional environments of AML cells, including genes involved in haematopoiesis and leukaemia. Furthermore, we show that elevated miR-155 expression detected in paediatric AML correlates with intermediate and not high miR-155 expression identified in our experimental models. These findings collectively describe a novel dose-dependent role for miR-155 in the regulation of AML, which may have important therapeutic implications.Leukemia advance online publication, 18 November 2016; doi:10.1038/leu.2016.279.en© 2016, Springer NatureAcute myeloid leukaemia; cancer genetics; cell biology; gene expression; miRNAsJournal article003005677410.1038/leu.2016.2790003982618000042-s2.0-84995753067274791Goodall, G. [0000-0003-1294-0692]