In vitro cytotoxicity of deferoxamine on human marrow haematopoietic progenitors

Deferoxamine (DFO), a widely used clinical chelator of ferric iron, was found to inhibit human bone-marrow (BM) stem-cell colony formation as measured by assays on the proliferation of the haematopoietic progenitor cell populations: the granulocyte-macrophage, colony forming unit in culture (CFU-C) lineage and the erythroid lineages-erythroid colony forming unit (CFU-E) and erythroid burst forming unit (BFU-E). DFO (5-20 μm) markedly reduced the proliferation of CFU-C, CFU-E and BFU-E in a dose-dependent fashion, whereas ferrioxamine, the chelated form of DFO, had no effect on colony growth. CFU-E and BFU-E colonies were more sensitive than CFU-C to the growth-inhibitory effect of DFO. The removal of either adherent cells or T lymphocytes or both from the BM did not affect the inhibitory properties of DFO, indicating that DFO interacts directly with the haematopoietic progenitor cells rather than through another cell population. These in vitro findings suggest that DFO may cause myelosuppression if administered to patients whose plasma iron levels are normal or low.