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

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• 作者：Vinod Pullarkat^a ; ^{vinod.pullarkat@med.usc.edu} ; Arjun Sehgal^a ; Liang Li^a ; Zhuo Meng^b ; Allen Lin^a ; Stephen Forman^a ; Ravi Bhatia^a
• 关键词：Myelodysplastic syndrome ; Hematopoiesis ; Progenitors ; Iron chelators ; Deferasirox ; Reactive oxygen species
• 刊名：Leukemia Research
• 出版年：2012
• 期刊代码：186_01452126
• 类别：med
• 出版时间：August, 2012
• 卷：36
• 期：8
• 页码：966-973
• 文件大小：1552 K

摘要

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 渭M to 20 渭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 渭M DFX which increased with duration of exposure. Exposure to 20 渭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 渭M. We conclude that exposure to DFX results in dose-dependent inhibition of proliferation, and survival in MDS progenitors.