Molecular mechanism of emergence of clonal disorders in aplastic anemia
| Project/Area Number |
14570989
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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 | Kumamoto University |
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Principal Investigator |
HORIKAWA Kentaro Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Research Associate, 大学院・医学薬学研究部, 助手 (40322309)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAKUMA Hideki Wakayama Medical University, Department of Hematology and Transfusion Service, Professor, 輸血・血液疾患治療部, 教授 (90207746)
KAWAGUCHI Tatsuya Kumamoto University, Kumamoto University Hospital, Assistant Professor, 医学部附属病院, 講師 (50244116)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | aplastic anemia / mutation / HPRT / PNH / 遺伝子変異 / 発作性夜間血色素尿 / 骨髄異形成症候群 |
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| Research Abstract |
Aplastic anemia (AA) is an disorder characterized with both pancytopenia and hypoplastic bone marrow. Although the etiology of the intractable disease is not still well known, hematopoietic progenitor cells are severely injured. Mutant clones infrequent emerge in this disease, and may develop to paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic anemia, and leukemia. To clarify molecular mechanism of the emergence of mutant clones, mutant frequency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) as an indicater of gene mutation among was detected among T cells from AA patiens.
1)HPRT mutation frequency
Peripheral mononuclear cells were obtained from AA patiens. The cells were cultured under both phytohemagglutinin and interleukin-2. Two weeks later, T cell colonies were observed. Cloning efficiency of the colonies ranged from 6-37% (mean 14%) among 9 patients with AA, and 9-33% (mean 18%) in 14 healthy volunteers. HPRT mutation frequency are detected by resistance of the mutant cells to culture condition containing 6-thioguanine. The results showed that the frequency of AA patients ranged 9.6x10^<-6>-2.3x10^<-4> (mean 6.8x10^<-5>) and 1.6x10^<-6>-3.7x10^<-5> (mean 1.3x10^<-5>) in healthy voluntees. The HPRT mutation frequency was 5-times higher in Aapatints than control.
2)Comparison to PNH
PNH is closely associated with AA in both etiology and clinical feature. We reported the high frequency of HPRT mutation in peripferal Tcells and bone marrow progenitor cells. To compare the frequency between AA and PNH, the frequency of PNH patients were detected simultaneously. The fmean requency of PNH 4 patients was 4.2x10^<-5>. Both PNH and AA patients showed higher frequency than control. These results suggest that abnormal condition in both AA and PNH may exists that favors the emergence of somatic mutations among hematopoietic cells.
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Report
(3 results)
Research Products
(11 results)
