The role of the tumor suppressor gene WT1 in human leukemogenesis.

• Project/Area Number: 11470210
• Research Category: Grant-in-Aid for Scientific Research (B).
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: SUGIYAMA Haruo Osaka University Medical School, Professor, 医学部, 教授 (70162906)
• Co-Investigator(Kenkyū-buntansha): SOMA Toshihiro Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助手 (40273619) ; OKA Yoshihiro Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助手 (20273691) ; OGAWA Hiroyasu Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (80194447) ; OJI Yusuke Osaka University Medical School, Associate Professor, 医学部, 助手 (20294100)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥14,500,000 (Direct Cost: ¥14,500,000); Fiscal Year 2000: ¥5,300,000 (Direct Cost: ¥5,300,000); Fiscal Year 1999: ¥9,200,000 (Direct Cost: ¥9,200,000)
• Keywords: leukemia / The WT1 gene / apoptosis / WT1 / tumor suppressor gene / oncogene / WWドメイン

Research Abstract

1. The wild-type WT1 gene was expressed in not only leukemia but also solid tumors, including lung cancers. The growth of these cancer cells was inhibited by the treatment with WT1 antisense oligomers.
2. Leukemic cell line K562 was arrested at G_2/M checkpoint by the treatment with WT1 antisense oligomers.
3. We have established the method to measure individually four different splicing variants (17AA+/KTS+, 17AA+/KTS-, 17AA-/KTS+, 17AA-/KTS-). By using this method, it was found that a 17AA+/KTS+ transcript was major in leukemic cells.
4. When the wild-type WT1 gene was transfected into myeloid progenitor cell 32D and the gene was constitutively expressed, the apoptosis of the 32D cells was inhibited.
5. A novel WT1-binding protein was cloned and named as WTIP was localized in splicesome and so considered as a splicing factor.

Research Products

• [Publications] Tsuboi,A. et al.: "The Wilms' tumor gene : its oncogenic function and clinical application."Int.J.Hemaol,. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Harada,Y. et al.: "The WT1 expression in human testicular germ cell tumors."Mol.Urol. 3. 357-363 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tamaki,H. et al.: "The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes."Leukemia.. 13. 393-399 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsuboi,A. et al.: "Constitutive expression of the Wilms'tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF)."Leuk.Res.. 23. 499-505 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sako,M. et al.: "Abnormal expression of the Wilms' tumor gene WT1 in juvenile chronic myeloid leukemia and infantile monosomy 7 syndrome."Leuk.Res.. 22. 965-967 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Oji,Y. et al.: "Cytotoxic T lymphocyte responses elicited to Wilms' tumor gene WT1 product by DNA vaccination."Jpn.J.Cancer Res.. 90. 194-204 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsuboi, A.et al.: "The Wilms' tumor gene : its oncogenic function and clinical application."Int.J.Hemaol. (in press.).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Harada, Y.et al.: "The WT1 expression in human testicular germ cell tumors."Mol.Urol. 3. 357-363 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tamaki, H.et al.: "The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes."Leukemia. 13. 393-399 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsuboi, A.et al.: "Constitutive expression of the Wilms' tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF)."Leuk.Res. 23. 499-505 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sako, M.et al.: "Abnormal expression of the Wilms' tumor gene WT1 in juvenile chronic myeloid leukemia and infantile monosomy 7 syndrome."Leuk.Res. 22. 965-967 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Oji, Y.et al.: "Cytotoxic T lymphocyte responses elicited to Wilms' tumor gene WT1 product by DNA vaccination."Jpn.J.Cancer Res. 90. 194-204 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sugiyama,H. et al.: "The Wilms' tumor gene : its oncogenic function and clinical application."Int.J.Hemaol,. (in press).
• [Publications] Harada,Y. et al.: "The WT1 expression in human testicular germ cell tumors."Mol.Urol.. 3. 357-363 (1999)
• [Publications] Tamaki,H. et al.: "The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes."Leukemia.. 13. 393-399 (1999)
• [Publications] Tsuboi,A. et al.: "Constitutive exptession of the Wilms' tumor gene WT1 inhibits the differentiation of myeloid progenito cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF)."Leuk.Res.. 23. 499-505 (1999)
• [Publications] Sako,M. et al.: "Abnormal expression of the Wilms' tumor gene WT1 in juvenile chronic myeloid leukemia and infantile monosomy 7 syndrome."Leuk.Res.. 22. 965-967 (1999)
• [Publications] Oji,Y. et al.: "Expression of the Wilms' tumor gene WT1 solid tumors and its essential role in tumor cell growth."Jpn.J.Cancer Res.. 90. 194-204 (1999)
• [Publications] Tsuboi A.et al.: "Constitutive expression of the Wilms' tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes then proliferation in response to granulocyte-colony stimulating factor(G-CSF)"Leukemia Research. 23. 499-505 (1999)
• [Publications] Oji Y.et al.: "Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth"Japanese Journal of Cancer Research. 90. 194-204 (1999)
• [Publications] Yamagami T.et al.: "Suppression of Wilms' tumor gone (WT1) expression induces G_2/M arrest in leukemic cells"Leukemia Research. 30. 55-61 (1998)
• [Publications] Inoue K.et al.: "Wilms' tumor gone (WT1)competes with differentiation-inducing signal in hematopoietic progenitor cells"Blood. 91. 2969-2976 (1998)