1997 Fiscal Year Final Research Report Summary
Functional analysis of the Wilms' tumor suppressor gene WT1 in hematopoiesis.
| Project/Area Number |
08671216
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
MIYAGAWA Kiyoshi Research Institute for Radiation Biology and Medicine, Hiroshima University, Professor, 原爆放射能医学研究所, 教授 (40200133)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Shigeru Faculty of Medicine, University of Tokyo, Research Associate, 医学部・附属病院, 助手 (60212049)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Transcription factor / Leukemia / Tmuor suppressor gene / Wilms' tumor |
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| Research Abstract |
Since the Wilms' tumor suppressor gene WTI is expressed in CD34-positive blood stem cells and leukemia, it is probable that WT1 is involved in leukemogenesis. To investigate if WT1 plays a role in leukemogenesis, we screend the WT1 gene from 20 cases of childhood acute myeloid leukemia for structural abnormality. SSCP analysis revealed band shifts suggesting the presence of mutations in three cases. Mutations were confirmed by direct sequencing. A His to Glin substitution at codon 397 was found in acute megakaryoblastic leukemia developed in a patient of the Down syndrome. A His to Leu substitution at codon 405 and an Arg to Gln at codon 394 were found in two cases of acute myeloid leukemia respectively. Thus WT1 mutations were found in 15% of acute myeloid leukemia. These mutations occurred in Zn finger domains, which are important for transcriptional regultion. All the cases carrying WT1 mutations exhibited a poor prognosis, one of which possessed the WT1 mutation at relapse but not at diagnosis. The chromosome translocation t (8 ; 21) was also found in a case with the WT1 mutation. These data strongly suggest that mutations in Zn finger domains of the WT1 gene are associated with the progression of acute myeloid leukemia.
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