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Myelodysplasias

High frequency of several PIG-A mutations in patients with aplastic anemia and myelodysplastic syndrome

Leukemia volume 20, pages 627–634 (2006)Cite this article

Abstract

To clarify some characteristics of phosphatidylinositol glycan-class A gene (PIG-A) mutations in aplastic anemia (AA) and myelodysplastic syndrome (MDS) patients compared with those in paroxysmal nocturnal hemoglobinuria (PNH) patients, we investigated PIG-A mutations in CD59− granulocytes and CD48− monocytes from seven AA, eight MDS, and 11 PNH Japanese patients. The most frequent base or type abnormalities of the PIG-A gene in AA and MDS patients were base substitutions or missense mutations, respectively, and deletions or frameshift mutations, respectively, in PNH patients. Several PIG-A mutations, most of which were statistically minor, were found in glycosylphosphatidylinositol-negative cells from all AA and MDS patients but not from all PNH patients. However, the common PIG-A mutations during the clinical course between CD59− granulocytes and/or CD48− monocytes from each AA or MDS patient, except for Case 5, were not found. PIG-A mutations were different between the granulocytes and monocytes from five AA and five MDS patients. Our results indicate that there were some characteristics of PIG-A mutations in AA and MDS patients compared with PNH patients and that several minor PNH clones in these patients occurred at random during the clinical course. This partly explains the transformation of AA or MDS to PNH at intervals.

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Acknowledgements

We thank Dr Teizo Fujita (Department of Biochemistry II, Fukushima Medical University, Japan), Dr Mitsuru Munakata (Department of Pulmonary Medicine, Fukushima Medical University, Japan), Dr Ikuo Wada (Department of Cell Science, Institute of Biomedical Science, Fukushima Medical University, Japan), and Ms Sayuri Mizuno (Fukushima Medical University, Japan) for their valuable assistance. We are also grateful to Dr Kazuei Ogawa (Fukushima Medical University, Japan), Dr Kenji Nagata, Dr Yurie Saitoh, Dr Hiroyuki Kanbayashi and Dr Shin Matsuda (Ohta Nishino-uchi Hospital, Japan), Dr Tatsuyuki Kai and Dr Hideo Kimura (General Hobara-chuoh Hospital, Japan), Dr Rokuo Abe (Fukushima-ken Taiyo-no-kuni Hospital, Japan), Dr Masayuki Mita (Hoshi General Hospital, Japan), and Dr Kenichi Nakamura (Shirakawa-kosei Hospital, Japan) for providing the samples from patients with AA and MDS. We are indebted to Dr Yuji Sugita (Showa University, Japan), who provided the monoclonal antibody to CD59/membrane attack complex-inhibitory factor.

This study was supported in part by a Grant-in-aid for Medical Research from the Fukushima Prefectural Hospitals (No. 160) and a Grant-in-aid from the Fukushima Society for the Promotion of Medicine (No. 14–32) to TS.

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Authors and Affiliations

  1. First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan

    M Okamoto, T Shichishima, H Noji, K Ikeda, A Nakamura, K Akutsu & Y Maruyama

  2. Fukushima Research Institute of Environment and Medicine, Fukushima, Japan

    T Shichishima

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  1. M Okamoto
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  2. T Shichishima
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Correspondence to T Shichishima.

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Okamoto, M., Shichishima, T., Noji, H. et al. High frequency of several PIG-A mutations in patients with aplastic anemia and myelodysplastic syndrome. Leukemia 20, 627–634 (2006). https://doi.org/10.1038/sj.leu.2404135

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