1998 Fiscal Year Final Research Report Summary
Analysis of roles of tumor suppressor gene WT1 in human leukemogenesis.
| Project/Area Number |
09470230
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
SUGIYAMA Haruo Osaka University Medical School, Professor, 医学部, 教授 (70162906)
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| Co-Investigator(Kenkyū-buntansha) |
SOMA Toshihiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (40273619)
OKA Yoshihiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (20273691)
OGAWA Hiroyasu Osaka University Medical School, Associate Professor, 医学部, 助教授 (80194447)
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| Project Period (FY) |
1997 – 1998
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| Keywords | WT1 / tumor suppressor gene / oncogene / 32D cells / hematopoietic progenitor cells |
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| Research Abstract |
The Wilms' tumor gene WT1 was identified as a gene responsible for Wilms' tumor, a childhood kidney neoplasm and classified as a tumor suppressor gene. The WT1 gene encoding a zinc finger transcription factor represses transcription of growth factors, p growth factor receptors and some other genes. We have reported high levels of wild-type WT1 expression in fresh leukemic cells regardless of the types of leukemias. Furthermore, WT1 antisense oligomer specifically inhibited the growth of leukemia cells. These results have raised a hypothesis that the wild-type WT1 gene exerts an oncogenic rather than a tumor suppressor gene function in hematopoietic progenitor cells and plays an important role in leukemogenesis. To prove this hypothesis, a series of experiments were performed. 32D c13, an interleukin 3-dependent myeloid progenitor cell line, differentiates into mature neutrophils in response to G-CSF.However, when transfected wild-type WT1 gene was constitutively expressed in 32D c13 cells, the cells stopped differentiating and continued to proliferate in response to G-CSF.Furthermore, significantly more CFU-GM, CFU-G, and CFU-M colonies were formed in WP1-infected bone marrow (BM) cells than in control BM cells in response to G-CSF.These results supported our hypothesis.
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[Publications] Inoue, K., Ogawa, H., Sonoda, Y., Kimura, T., Sakabe, H., Oka, Y., Miyake, S., Tamaki、H., Oji, Y., Yamagami, T., Tatekawa, T., Soma, T., Kishimoto, T., and Sugiyama, H.: "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
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[Publications] Sugiyama, H., Inoue, K., Soma, T., Tamaki, H., Oka, Y., Ogawa, H., and Kishimoto: "T.Wilms tumor gene (WT1) mRNA is equally expressed in blast cells from acute myeloid leukemia and normal CD34^+ progenitors (Response)." Blood. 90. 4230-4232 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Inoue, K., Tamaki, H., Ogawa, H., Oka, Y., Soma, T., Tatekawa, T., Oji, Y., Tsuboi, A., Kim, E.H., Kawakami, M., Akiyama, T., Kishimoto, T., and Sugiyama, H.: "Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells." Blood. 91. 2969-2976 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yamagami, T., Ogawa, H., Tamaki, H., Oji, Y., Soma, T., Oka, Y., Tatekawa, T., Tsuboi, A., Kim, E.H., Akiyama, T., and Sugiyama, H.: "Suppression of Wilms'tumor gene (WT1) expression induces G_2/M arrest in leukemic cells." Lekemia Research. 22. 383-384 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Tsuboi, A., Oka, Y., Ogawa, H., Elisseeva, A.A., Tamaki, H., Oji, Y., Kim, E.H., Soma, T., Tatekawa, T., Kawakami, M., Kishimoto, T., and Sugiyama, H.: "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)." Leukemia Research. (in press).
Description
「研究成果報告書概要(欧文)」より
