miR-486 is a regulator of normal erythropoiesis and myeloid leukemogenesis. (A) Expression pattern of miR-486 in normal and malignant hematopoiesis. (B) miR-486 expression is upregulated during erythroid differentiation (left), and forced overexpression of miR-486 in hematopoietic stem and progenitor cells pushes the expansion of erythrocyte differentiation (right). miR-486 expression directly controls PTEN and FoxO1 to permit activation of AKT signaling during normal erythroid differentiation. (C) Overexpression of miR-486 cooperates with Gata1s to increase proliferation and self-renewal, and knockdown of miR-486 in ML-DS induces cell death (left). Expression of miR-486 synergizes with BCR-ABL to promote cell proliferation (right). Imatinib treatment of CML cells partly reduces miR-486 expression and induces cell death, which is amplified by sponge-mediated knockdown of miR-486. EPO, erythropoietin; HSC, hematopoietic stem cell; HSPC, hematopoietic stem and progenitor cell; NDS, non-DS.