Schematic representation of a model for the role of miR-223, C/EBPα, and E2F1 in normal granulopoiesis and in AML. During granulopoiesis (top panel), C/EBPα binds and transactivates miR-223 promoter, which in turn leads to E2F1 repression and inhibition of cell-cycle progression resulting in myeloid differentiation. When C/EBPα is deregulated by various mechanisms in AML (bottom panel), transactivation of miR-223 is inhibited, which results in accumulation of E2F1. Overexpressed E2F1 binds to miR-223 promoter and inhibits miR-223 transcription through a negative feedback loop resulting in myeloid cell-cycle progression and block of differentiation.