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

We recently showed that moderate hypoxia and hypoxia-mimetic agents CoCl2 and desferrioxamine (DFO) induce differentiation of acute myeloid leukemic cells via hypoxia-inducible factor-1α (HIF-1α) that interacts with and increases the transcriptional activity of CCAAT/enhancer-binding protein α (C/EBPα), a critical factor for granulocytic differentiation. Here, we show that metavanadate antagonizes DFO-induced growth arrest and differentiation with the inhibition of HIF-1α protein accumulation in leukemic cells. Furthermore, DFO also increased C/EBPα expression rapidly but transiently, which was inhibited by metavanadate. Taken together, these findings provide further evidence for the role of HIF-1α and C/EBPα in DFO-induced leukemic cell differentiation.