A Study on development and clonality of PIG-A mutant clones in paroxysmal nocternal hemoglobinuria
| Project/Area Number |
08671233
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
MACHII Takashi (1997) Osaka University Medical School, Associate Professor, 医学部, 助教授 (50124780)
徳嶺 進洋 (1996) 大阪大学, 医学部, 助手 (90207564)
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| Co-Investigator(Kenkyū-buntansha) |
KANAKURA Yuzuru Osaka University Medical School, Assistant Professor, 医学部, 教授 (20177489)
MIZUKI Masao Osaka University Medical School, Assistant Professor, 医学部, 助手 (80283761)
木谷 照夫 大阪大学, 医学部, 名誉教授 (80028406)
待井 隆志 大阪大学, 医学部, 助教授 (50124780)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | paroxysmal nocturnal hemoglobinuria / PIG-A gene / clonality / Aplactic aremia / mutation frequency / glycophonn A / GPIアンカー型蛋白 / CD59 / HUMARA遺伝子 / 遺伝子不安定性 / サテライトマーカー |
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| Research Abstract |
1. Mutations of the PIG-A gene and clonality in PNH
We analyzed the PIG-A gene in two B-cell lines bearing complete or partial deficiencies, cells of hematopoietic progenitor colonies and peripheral blood granulocytes from a patient with PNH.Four independent PIG-A mutant clones were identified. Two mutations were shared by B-cells, erythroid- and myeloid-cells, one was shared by erythroid- and myeloid-cells, and the other one was only found in erythroid-cells. Our findings further show oligoclonal nature of PNH and differences in extent of expansion in each clone.
2. PIG-A gene analysis in CD59-deflcient blood cells from patients with AA
We examined expression of CD59 in patients with AA and found CD59-deficient blood cellsin 11 patients. Mutations of the PIG-A gene were detected by heteroduplex assay in 10 of the 11 patients. Nucleotide changes were determined in six cases. They were all different, and most showed small mutations. There appears to be no difference in the patterns of the mutations between AA with CD59-deficiency and de novo PNH.
3. Mutation frequency in PNH and AA
In vitro mutation frequencies were investigated in PNH and AA by erythrocyte glycophorin A mutation assay. The assay enumerates NO or NN variant cells in erythrocytes of the MN type. Abnormal events in the NO variants were detected in 4 of 9 PNH cases and 2 of 9 AA cases, and those in the NN variants were found in 2 of 9 cases in PNH and AA, respectively. Our finding that mutation frequencies are increased in a proportion of the patients suggest that genes including the PIG-A gene are unstable and/or have been exposed mutagenic pressure. Increased mutation frequency may be associated with development of the PIG-A gene abnormality in these disorders.
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Report
(3 results)
Research Products
(13 results)
