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Chromosomal instability and radiosensitivity in myelodysplastic syndrome cells

Leukemia volume 16, pages 2253–2258 (2002)Cite this article

Abstract

Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells. To investigate whether chromosomal instability and/or DNA repair defects are involved in the development of MDS, we measured the micronucleus (MN) frequency in peripheral blood lymphocytes exposed to various doses of X-rays, using a cytokinesis-block micronucleus assay. The spontaneous MN frequencies in RAEB and RAEB-T patients were significantly higher than those in normal individuals (P = 0.0224, P = 0.008, respectively). Also, the X-ray-induced MN frequencies in RA/RARS, RAEB, and RAEB-T patients were significantly higher than those in normal individuals (P = 0.007, P = 0.003, P = 0.003, respectively, at 2 Gy). In order to elucidate the cause of unusual radiosensitivity, we measured the expression levels of nucleotide excision repair (NER) genes in peripheral blood mononuclear cells using a RT-PCR method. Reduction of NER gene expression was found in only one of 10 patients with low risk MDS, but in four of 11 patients with high risk MDS. Our data suggest that chromosomal instability and DNA repair defects may be involved in the pathophysiology of disease progression of MDS.

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Acknowledgements

We thank Dr Nobutaka Imamura, Research Institute for Radiation Biology and Medicine, Hiroshima University, and Dr Seishi Kyoizumi, Radiation Effects Research Foundation, for valuable discussions and suggestions.

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Authors and Affiliations

  1. Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan

    K Kuramoto & G Suzuki

  2. Frontier Research Center, National Institute of Radiological Sciences, Chiba, Japan

    S Ban

  3. Department of Internal Medicine, Hiroshima City Hospital, Hiroshima, Japan

    K Oda

  4. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    H Tanaka & A Kimura

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Kuramoto, K., Ban, S., Oda, K. et al. Chromosomal instability and radiosensitivity in myelodysplastic syndrome cells. Leukemia 16, 2253–2258 (2002). https://doi.org/10.1038/sj.leu.2402703

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