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

TLDR

MicroRNAs are key regulators of immune system development and function. Enforced miR‑155 expression in mouse bone marrow drives granulocyte/monocyte proliferation and induces myeloid‑neoplasia–like pathology, mirroring LPS‑induced expansion, and is overexpressed in AML, underscoring its role in normal and malignant myelopoiesis.

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-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.