We recently showed that moderate hypoxia and hypoxia-minietic agents CoCl, and desferrioxamine (DFO) induce differentiation of acute myeloid leukemic cells via hypoxia-inducible factor-1 alpha (HIF-1 alpha) that interacts with and increases the transcriptional activity of CCAAT/enhancer-binding protein alpha (C/EBP alpha), a critical factor for granulocytic differentiation. Here, we show that metavanadate antagonizes DFO-induced growth arrest and differentiation with the inhibition of HIF-1 alpha protein accumulation in leukemic cells. Furthermore, DFO also increased C/EBP alpha expression rapidly but transiently, which was inhibited by metavanadate. Taken together, these findings provide further evidence for the role of HIF-1 alpha and C/EBP alpha in DFO-induced leukemic cell differentiation. (c) 2005 Elsevier Inc. All rights reserved.