title: Deferasirox exposure induces reactive oxygen species and reduces growth and viability of myelodysplastic hematopoietic progenitors.
abstract: 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 μM to 20 μM. 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 μM DFX which increased with duration of exposure. Exposure to 20 μM 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 μM. We conclude that exposure to DFX results in dose-dependent inhibition of proliferation, and survival in MDS progenitors.
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA, USA. vinod.pullarkat@med.usc.edu
authors.forename: Vinod
authors.initials: V
authors.lastname: Pullarkat
authors.forename: Arjun
authors.initials: A
authors.lastname: Sehgal
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Meng
authors.forename: Allen
authors.initials: A
authors.lastname: Lin
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.forename: Ravi
authors.initials: R
authors.lastname: Bhatia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000077588:Deferasirox; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D014230:Triazoles; D000077588:Deferasirox