Deferasirox exposure induces reactive oxygen species and reduces growth and viability of myelodysplastic hematopoietic progenitors

We examined the effect of deferasirox (DFX) on CD34+ hematopoietic progenitors from MDS patients. Progressive, dose-dependent suppression of MDS progenitor proliferation in culture was observed with DFX concentrations ranging from 5 mu M to 20 mu M. This effect was more pronounced in MDS compared to CD34+ progenitors isolated from umbilical cord blood or normal peripheral blood. There was reduced viability of MDS progenitors but not normal progenitors at 20 mu M DFX which increased with duration of exposure. Exposure to 20 mu M DFX for 14 days markedly suppressed colony growth of MDS progenitors. Reactive oxygen species levels were elevated above control at concentrations of DFX above 5 mu M. We conclude that exposure to DFX results in dose-dependent inhibition of proliferation, and survival in MDS progenitors. (C) 2012 Elsevier Ltd. All rights reserved.