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01-02-2012 | Original Article

The effect of iron overload and chelation on erythroid differentiation

Authors: Kazuki Taoka, Keiki Kumano, Fumihiko Nakamura, Masataka Hosoi, Susumu Goyama, Yoichi Imai, Akira Hangaishi, Mineo Kurokawa

Published in: International Journal of Hematology | Issue 2/2012

Abstract

We investigated the mechanisms of hematopoietic disorders caused by iron overload and chelation, in particular, the inhibition of erythroblast differentiation. Murine c-kit⁺ progenitor cells or human CD34⁺ peripheral blood hematopoietic progenitors were differentiated in vitro to the erythroid lineage with free iron and/or an iron chelator. Under iron overload, formation of erythroid burst-forming unit colonies and differentiation to mature erythroblasts were significantly suppressed; these effects were canceled by iron chelation with deferoxamine (DFO). Moreover, excessive iron burden promoted apoptosis in immature erythroblasts by elevating intracellular reactive oxygen species (ROS). Interestingly, both DFO and a potent anti-oxidant agent reduced intracellular ROS levels and suppressed apoptosis, thus restoring differentiation to mature erythroblasts. Accordingly, intracellular ROS may represent a new therapeutic target in the treatment of iron overload.

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Title: The effect of iron overload and chelation on erythroid differentiation
Authors: Kazuki Taoka
Keiki Kumano
Fumihiko Nakamura
Masataka Hosoi
Susumu Goyama
Yoichi Imai
Akira Hangaishi
Mineo Kurokawa
Publication date: 01-02-2012
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 2/2012
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-011-0988-3

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