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Loss of ABCB7 gene: pathogenesis of mitochondrial iron accumulation in erythroblasts in refractory anemia with ringed sideroblast with isodicentric (X)(q13)

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Abstract

An isodicentric (X)(q13) (idicXq13) is a rare, acquired chromosomal abnormality originated by deletion of the long arm from Xq13 (Xq13-qter), and is found in female patients with hematological disorders involving increased ringed sideroblasts (RSs), which are characterized by mitochondrial iron accumulation around the erythroblast nucleus. The cause of increased RSs in idicXq13 patients is not fully understood. Here, we report the case of a 66-year-old female presenting with refractory anemia with ringed sideroblasts (RARS), and idicXq13 on G-banded analysis. We identify the loss of the ABCB7 (ATP-binding cassette subfamily B member-7) gene, which is located on Xq13 and is involved in mitochondrial iron transport to the cytosol, by fluorescent in situ hybridization (FISH) analysis and the decreased expression level of ABCB7 mRNA in the patient’s bone marrow cells. Further FISH analyses showed that the ABCB7 gene is lost only on the active X-chromosome, not on the inactive one. We suggest that loss of ABCB7 due to deletion of Xq13-qter at idicXq13 formation may have contributed to the increased RSs in this patient. These findings suggest that loss of the ABCB7 gene may be a pathogenetic factor underlying mitochondrial iron accumulation in RARS patients with idicXq13.

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Authors and Affiliations

  1. Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan

    Kazuya Sato, Takaaki Hosoki, Katsuya Ikuta, Masayo Yamamoto, Satoshi Ito, Naoka Okamura, Kazuhiko Ichiki, Hiroki Tanaka, Motohiro Shindo, Yusuke Mizukami, Takaaki Otake, Mikihiro Fujiya, Kastunori Sasaki & Yutaka Kohgo

  2. Oncology Center, Asahikawa Medical University Hospital, Asahikawa, Hokkaido, Japan

    Yoshihiro Torimoto

  3. Department of Medical Laboratory and Blood Center, Asahikawa Medical University Hospital, Asahikawa, Hokkaido, Japan

    Hiroyuki Takahashi

  4. Kamifurano Town Hospital, Kamifurano, Hokkaido, Japan

    Katsuyuki Hirai

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  1. Kazuya Sato
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  2. Yoshihiro Torimoto
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  14. Takaaki Otake
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  16. Kastunori Sasaki
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Correspondence to Kazuya Sato.

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Sato, K., Torimoto, Y., Hosoki, T. et al. Loss of ABCB7 gene: pathogenesis of mitochondrial iron accumulation in erythroblasts in refractory anemia with ringed sideroblast with isodicentric (X)(q13). Int J Hematol 93, 311–318 (2011). https://doi.org/10.1007/s12185-011-0786-y

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  • DOI: https://doi.org/10.1007/s12185-011-0786-y

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