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Molecular Diagnosis of Human Leukemias

Research Project

Project/Area Number 04253208
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionUniversity of Tokyo

Principal Investigator

HIRAI Hisamaru  University of Tokyo, 3rd Dept.of Internal Med., Lecturer, 医学部(病), 講師 (90181130)

Co-Investigator(Kenkyū-buntansha) OGAWA Seishi  University of Tokyo, 3rd Dept.of Internal Med., Medical Fellow, 医学部(病), 医員
MITANI Kinuko  University of Tokyo, 3rd Dept.of Internal Med., Assistant Pro., 医学部(病), 助手 (50251244)
杉本 耕一  東京大学, 医学部(病), 医員
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥19,000,000 (Direct Cost: ¥19,000,000)
Fiscal Year 1993: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1992: ¥9,000,000 (Direct Cost: ¥9,000,000)
Keywordst(3 ; 21) translocation / chronic myelocytic leukemia / blastic crisis / AML1 / EVI-1 chimeric gene / AML1 gene / EVI-1 gene / transcription factor / N-ras遺伝子 / p53遺伝子 / Ph^1陽性ALL / CML急性転化 / 骨髄異形成症候群 / 白血病 / SSCP法 / PCR法
Research Abstract

The t(3 ; 21)(q26 ; q22) translocation is thought to trigger blastic crisis in chronic myelocytic leukemia (CML). This reciprocal translocation generates an AML1/EVI-1 chimeric gene which is transcribed as fusion mRNAs. The 180 kD AML1/EVI-1 fusion protein contains an amino-terminal half of AML1 including a runt homology domain which is fused to the entire of zinc finger EVI-1 protein. The AML1/EVI-1 fusion transcript is consistent among all three cases of the t(3 ; 21)-carrying leukemia examined. Synthetic antisense oligonucleotides complementary to the sequences including the transcriptional initiation sequences of authentic AML1 and EVI-1 specifically suppress growth of leukemia cells with the t(3 ; 21) translocation. These findings strongly suggest that the t(3 ; 21) translocation results in the formation of a new class of a chimeric transcription factor which could contribute to leukemic progression through interference with cell growth and differentiation.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Toyoshima H: "Differently spliced cDNAs of human ltk receptor tyrosine kinase predeict receptor proteins with and without tyrosine kinase domain and a soluble receptor protein." Proc.Natl.Acad.Sci.USA. 90. 5404-5408 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sugimoto K: "Mutations of the p53 gene in myelodysplastic syndromes and MDS-derived leukemia." Blood. 81. 3022-3026 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hanazono Y: "c-fps/fes protein-tyrosine kinase is implicated in a signaling pathway triggered by granulocyte-macrophage colony-stimulating factor and interleukin-3." EMBO J.12. 1641-1646 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ogawa S: "Detection of the PML/RAR α fusion gene in acute promyelocytic leukemia with a complex translocation involving chromosome 15,17,and 18." Cancer Genet.Cytogenet.69. 113-117 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Amano M: "Rearrangement of retinoic acid receptor α and PML in promyelocytic blast crisis of Ph1 chromosome positive chronic myelocytie leukemia with normal copies of chromosome 15." Blood. 81. 2469-2470 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mitani K: "Generation of the AML1/Evi-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Toyoshima H,Kozutsumi H,Maru Y,Hagiwara K,Furuya A,Mioh H,Hanai N,Takaku F,Yazaki Y,Hirai H: "Differently spliced cDNAs of human 1tk receptor tyrosine kinase predict receptor proteins with and without tyrosine kinase domain and a soluble receptor protein" Proc.Natl.Acad.Sci.USA. 90. 5404-5408 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sugimoto K,Hirano N,Toyoshima H,Chiba S,Mano H,Takaku F,Yazaki Y,Hirai H: "Mutations of the p53 gene in myelodysplastic syndromes and MDS-derived leukemia" Blood. 81. 3022-3026 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hanazono Y,Chiba S,Sasaki K,Mano H,Miyajima A,Arai K,Yazaki Y,Hirai H: "c-fps/fes protein-tyrosine kinase is implicated in a signaling pathway triggered by granulocyte-macrophage colony-stimulating factor and interleukin-3" EMBO J.12. 1641-1646 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hanazono Y,Chiba S,Sasaki K,Mano H,Yazaki Y,Hirai H: "Erythropoietin induces tyrosine phosphorylation and kinase activity of the c-fps/fes proto-oncogene product in human erythropoietin-responsive cells" Blood. 81. 3193-3196 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sasaki K,Chiba S,Hanazono Y,Mano H,Yazaki Y,Hirai H: "Coordinate expression of the alpha and beta chains of human granolocyte-macrophage colony-stimulating factor receptor confers ligand-induced morphological transformation in mouse fibroblasts" J.Biol.Chem.268. 13697-13702 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ogawa S,Mitani K,Sato Y,Sugimoto K,Toyoshima H,Mano H,Takaku F,Yazaki Y,Hirai H: "Detection of the PML/RARalpha fusion gene in acute promyelocytic leukemia with a complex translocation involving chromosome 15,17, and 18" Cancer Genet.Cytogenet.69. 113-117 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Amano M,Togawa A,Tsurugano S,Soda Y,Yuo A,Takaku F,Ogawa S,Hirai H,Yamada K: "Rearrangement of retinoic acid receptor alpha and PML in promyelocytic blast crisis of Phl chromosome positive chronic myelocytic leukemia with normal copies of chromosome 15" Blood. 81. 2469-2470 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mitani K,Ogawa S,Miyoshi H,Kurokawa M,Mano H,Yazaki Y,Ohki M,Hirai H: "Generation of the AML1/Evi-1 fusion gene in the t(3 ; 21)(q26 ; q22) causes blastic crisis in chronic myelocytic leukemia" EMBO. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Toyoshima H: "Differently spliced cDNAs of human Itk receptor tyrosine kinase predict receptor proteins with and without tyrosine kinase domain and a soluble receptor protein." Proc.Natl.Acad.Sci.USA. 90. 5404-5408 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugimoto K: "Mutations of the p53 gene in myelodysplastic syndromes and MDS-derived leukemia." Blood. 81. 3022-3026 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hanazono Y: "c-fps/fes protein-tyrosine kinase is implicated in a signaling pathway triggered by granulocyte-macrophage colony-stimulating factor and interleukin-3." EMBO J.12. 1641-1646 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogawa S: "Detection of the PML/RARα fusion gene in acute promyelocytic leukemia with a complex translocation involving chromosome 15,17,and 18." Cancer Genet.Cytogenet.69. 113-117 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Amano M: "Rearrangement of retinoic acid receptor α and PML in promyelocytic blast crisis of Ph1 chromosome positive chronic myelocytic leukemia with normal copies of chromosome 15." Blood. 81. 2469-2470 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mitani K: "Generation of the AML1/Evi-1 fusion gene in the t(3;21)(q26:q22)causes blastic crisis in chronic myelocytic leukemia."

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugimoto K et al.: "Freguent mutations in the p53 gene in human myeloid leukemia cell lines." Blood. 79. 2378-2383 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mitani K et al.: "Two myelodysplastic syndrome cases with the inv(11)(p15g23)as a sole chromosomal alonormality." Brit.J.Haematol.81. 512-515 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Toyoshima H et al.: "Differently spliced cDNAs of human ltk receptor tyrosine leinase predict receptor proteins with and without tyrosine leinase domain and a sduble receptor protein." Proc.Nacl.Acad.Sci.USA (In press).

    • Related Report
      1992 Annual Research Report
  • [Publications] Sugimoto K et al.: "Mutations of the p53 gene in myelodysplastic syndromes and MDS-derived leukemia." Blood(In press).

    • Related Report
      1992 Annual Research Report
  • [Publications] Hanazono Y et al.: "c-fps/fes protein-tyrosine kinase is implicated in a signaling pathway triggered by granulocyte-mecrophage colony-stimulating factor and IL-3" EMBO J.(In press).

    • Related Report
      1992 Annual Research Report
  • [Publications] Sasaki K et al.: "Coordinate expression of the α and β chains of human gramulocyte-macrophage colony-stimulating factor receptor confers ligand-induced morphological transformation in mouse fibroblases." J.Biol.Chem.(In press).

    • Related Report
      1992 Annual Research Report
  • [Publications] 平井 久丸他: "遺伝子からみた癌の病態と診断" 羊土社, 151 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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