Metavanadate suppresses desferrioxamine-induced leukemic cell differentiation with reduced hypoxia-inducible factor-1alpha protein.

We recently showed that moderate hypoxia and hypoxia-mimetic agents CoCl(2) and desferrioxamine (DFO) induce differentiation of acute myeloid leukemic cells via hypoxia-inducible factor-1alpha (HIF-1alpha) that interacts with and increases the transcriptional activity of CCAAT/enhancer-binding protein alpha (C/EBPalpha), a critical factor for granulocytic differentiation. Here, we show that metavanadate antagonizes DFO-induced growth arrest and differentiation with the inhibition of HIF-1alpha protein accumulation in leukemic cells. Furthermore, DFO also increased C/EBPalpha expression rapidly but transiently, which was inhibited by metavanadate. Taken together, these findings provide further evidence for the role of HIF-1alpha and C/EBPalpha in DFO-induced leukemic cell differentiation.