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1997 Fiscal Year Final Research Report Summary

Functional analysis of the Wilms' tumor suppressor gene WT1 in hematopoiesis.

Research Project

Project/Area Number 08671216
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionHIROSHIMA UNIVERSITY

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)

Co-Investigator(Kenkyū-buntansha) CHIBA Shigeru  Faculty of Medicine, University of Tokyo, Research Associate, 医学部・附属病院, 助手 (60212049)
Project Period (FY) 1996 – 1997
KeywordsTranscription factor / Leukemia / Tmuor suppressor gene / Wilms' tumor
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.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Miyagawa, K.: "Loss of WT1 function leads to ectopic myogenesis in Wilms' tumour" Nature Genetics. 18 (1). 15-17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hosoya, N.: "Frameshift mutations of the hMSH6 gene in human leukemia cell lines" Japanese Journal of Cancer Research. 89 (1). 33-39 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mitani, K.: "No concomitant occurrence of the N-ras and p53 gene mutations in myelodysplastic syndromes" Leukimia. 11. 863-865 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugimoto, K.: "Decreased or altered expression of the FHIT gene in human leukemias" Stem Cells. 15 (3). 223-228 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueno, H.: "The phosphatidylinositol 3' kinase pathway is required for the survival signal of leukocyte tyrosine kinase" Oncogene. 14. 3067-3072 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyagawa, K.: "Loss of WT1 function leads to ectopic myogenesis in Wilms' tumor." Nature Genetics. 18-1. 15-17 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hosoya, N.: "Frameshift mutations of the hMSH6 gene in human leukemia cell lines." Japanese Journal of Cancer Research. 89-1. 33-39 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitani, K.: "No concomitant occurrence of the N-ras and p53 gene mutations in myelodysplastic syndromes." Leukemia. 11. 863-865 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugimoto, K.: "Decreased or altered expression of the FHIT gene in human leukemia" Stem Cells. 15-3. 223-228 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueno, H.: "The phosphatidylinositol 3' kinase pathway is required for the survival signal of leukocyte tyrosine kinase." Oncogene. 14. 3067-3072 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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