Hu5F9-G4 binds human CD47 with tight affinity, blocks the CD47-SIRPα interaction, enables phagocytosis of primary AML cells in vitro, eliminates human AML in xenograft models, synergizes with rituximab in the eradication of NHL xenografts, and was safely administered intravenously to non-human primates at doses able to achieve serum levels much higher than the potential therapeutic range. Here, SIRPA is linked to acute myeloid leukemia.