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Role of the tumor suppressor gene WT1 in human leukemogenesis.

Research Project

Project/Area Number08457278
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

SUGIYAMA Haruo  Osaka Univ.Med.School, Dept.of Clin.Lab.Science, Professor, 医学部, 教授 (70162906)

Co-Investigator(Kenkyū-buntansha) MIYAKE Seigou  Osaka Univ.Hosptal.Staff, 医学部・附属病院, 医員
SOMA Toshihiro  Osaka Univ.Med.School, Dept.of Med.III,Assistant prof., 医学部, 助手 (40273619)
OKA Yoshihiro  Osaka Univ.Med.School, Dept.of Med.III,Assistant prof., 医学部, 助手 (20273691)
OGAWA Hiroyasu  Osaka Univ.Med.School, Dept.of Med.III,Lecturer, 医学部, 講師
Project Period (FY) 1996
Project Status Completed(Fiscal Year 1996)
Budget Amount *help
¥4,800,000 (Direct Cost : ¥4,800,000)
Fiscal Year 1996 : ¥4,800,000 (Direct Cost : ¥4,800,000)
KeywordsWT1 / Wilms tumor gene / leukemia
Research Abstract

To clarify whether the expression of the WT1 gene in leukemic cells is aberrant or merely reflects that in normal counterparts, the expression levels of the WT1 gene were quantitated for normal hematopoietic progenitor cells. Bone marrow (BM) and umbilical cord blood (CB) cells were fluorescence-activated cell sorting (FACS)-sorted into CD34^+ and CD34^- cell populations, and the CD34^+ cells into nine subsets (CD34^+CD33^-, CD34^+CD33^+.CD34^+CD38^-, CD34^+CD38^+, CD34^+HLA-DR^-, CD34^+HLA-DR^+, CD34^+c-kit^<hight>, CD34^+c-kit-^<low>, and CD34^+c-kit^-) according to the expression levels of CD34, CD33, CD38, HLA-DR,and c-kit. Moreover, acute myeloid leukemic cells were also FACS-sorted into four populations (CD34^+CD33^-, CD34^+CD33^+, CD34^-CD33^+, and CD34^-CD33^-). FACS-sorted normal hematopoietic progenitor and leukemic cells and FACS-unsorted leukemic cells were examined for the WT1 expression by quantitative reverse transcriptase-polymerase chain reaction. The WT1 expression in the CD34^+ and CD34^- cell populations and in the nine CD34^+ subsets of BM and CB was at either very low (1.0 to 2.4 x 10^<-2>) or undetectable (<10^<-2>) levels (the WT1 expression level of K562 cells was defined as 1.0), whereas the average levels of WT1 expression in FACS-sorted and-unsorted leukemic cells were 2.4 to 9.3 x 10^<-1>. Thus, the WT1 expression levels in normal hematopoietic progenitor cells were at least 10 times less than those in leukemic cells. Therefore, we could not find any normal counterparts of BM or CB that expressed the WT1 at levels comparable with those in leukemic cells. These results indicate an aberrant overexpression of the WT1 gene in leukemic cells and imply the involvement of this gene in human leukemogenesis.

Report

(2results)
  • 1996 Annual Research Report   Final Research Report Summary

Research Products

(12results)

All Other

All Publications

  • [Publications] Inoue, K., et al.: "Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels." Blood. 88. 2267-2278 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamagami., T., et al.: "Growth inhibition of human leukemic cells by WT1 (Wilms tumor gene) antisense oligodeoxynucloetides : Implications for the involvement of WT1 in leukemogenesis." Blood. 87. 2878-2884 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tamaki, H., et al.: "Increased expression of the Wilms tumor (WT1) at relapse in acute leukemia." Blood. 88. 4396-4398 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue, K., et al.: "Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia." Blood. 89. 1405-1412 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue, K., et al.: "Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels" Blood. 88. 2267-2278 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamagami., T., et al.: "Growth inhibition of human leukemic cells by WT1 (Wilms tumor gene) antisense oligodeoxynucleotides : Implications for the involvement of WT1 in leukemogenesis" Blood. 87. 2878-2884 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tamaki, H., et al.: "Increased expression of the Wilms tumor gene (WT1) at relapse in acute leukemia" Blood. 88. 4396-4398 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue, K., et al.: "Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia" Blood. 89. 1405-1412 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue,K.,et al.: "Long-term follow-up of minimal residual disease in leukemia patients by monitoring WTI (Wilms tumor gene) expression levels." Blood. 88. 2267-2278 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamagami.,T.,et al.: "Growth inhibition of human leukemic cells by WTI (Wilms tumor gene) antisense oligodeoxynucleotides : Implicatins for the involvement of WT1 in leukemogenesis." Blood. 87. 2878-2884 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tamaki,H.,et al.: "Increased expression of the Wilms tumor gene (WT1) at relapse in acute leukemia." Blood. 88. 4396-4398 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inoue,K.,et al.: "Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia." Blood. 89. 1405-1412 (1997)

    • Related Report
      1996 Annual Research Report

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Published : 1996-04-01   Modified : 2016-04-21  

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