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The iron chelator deferasirox affects redox signalling in haematopoietic stem/progenitor cells
Author(s) -
Tataranni Tiziana,
Agriesti Francesca,
Mazzoccoli Carmela,
Ruggieri Vitalba,
Scrima Rosella,
Laurenzana Ilaria,
D'Auria Fiorella,
Falzetti Franca,
Di Ianni Mauro,
Musto Pellegrino,
Capitanio Nazzareno,
Piccoli Claudia
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13381
Subject(s) - deferasirox , haematopoiesis , stem cell , myelodysplastic syndromes , progenitor cell , microbiology and biotechnology , cd34 , cancer research , biology , bmi1 , deferoxamine , sox2 , reprogramming , immunology , bone marrow , biochemistry , cell , genetics , thalassemia , gene , transcription factor
Summary The iron chelator deferasirox ( DFX ) prevents complications related to transfusional iron overload in several haematological disorders characterized by marrow failure. It is also able to induce haematological responses in a percentage of treated patients, particularly in those affected by myelodysplastic syndromes. The underlying mechanisms responsible for this feature, however, are still poorly understood. In this study, we investigated the effect of DFX ‐treatment in human haematopoietic/progenitor stem cells, focussing on its impact on the redox balance, which proved to control the interplay between stemness maintenance, self‐renewal and differentiation priming. Here we show, for the first time, that DFX treatment induces a significant diphenyleneiodonium‐sensitive reactive oxygen species ( ROS ) production that leads to the activation of POU5F 1 ( OCT 4 ), SOX 2 and SOX 17 gene expression, relevant in reprogramming processes, and the reduction of the haematopoietic regulatory proteins CTNNB 1 (β‐Catenin) and BMI 1. These DFX ‐mediated events were accompanied by decreased CD 34 expression, increased mitochondrial mass and up‐regulation of the erythropoietic marker CD 71 ( TFRC ) and were compound‐specific, dissimilar to deferoxamine. Our findings would suggest a novel mechanism by which DFX , probably independently on its iron‐chelating property but through ROS signalling activation, may influence key factors involved in self‐renewal/differentiation of haematopoietic stem cells.