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The effect of iron overload and chelation on erythroid differentiation

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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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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

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

  2. Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan

    Keiki Kumano & Mineo Kurokawa

Authors
  1. Kazuki Taoka
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  2. Keiki Kumano
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  3. Fumihiko Nakamura
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  4. Masataka Hosoi
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  5. Susumu Goyama
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  8. Mineo Kurokawa
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Correspondence to Mineo Kurokawa.

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Taoka, K., Kumano, K., Nakamura, F. et al. The effect of iron overload and chelation on erythroid differentiation. Int J Hematol 95, 149–159 (2012). https://doi.org/10.1007/s12185-011-0988-3

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  • DOI: https://doi.org/10.1007/s12185-011-0988-3

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