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Novel Hematopoietic Factors Produced by Human Undifferentiated Leukemia Cell Lines. and Their Biological Significance

Research Project

Project/Area Number 03404067
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

ASANO Shigetaka  The Inst. of Med. Sci., The Univ. of Tokyo Professor, 医科学研究所, 教授 (50134614)

Co-Investigator(Kenkyū-buntansha) TOJO Arinobo  The Inst. of Med. Sci., The Univ. of Tokyo Research Associate, 医科学研究所, 助手 (00211681)
IKEBUCHI Kenji  The Inst. of Med. Sci., The Univ. of Tokyo Lecturer, 医科学研究所, 講師 (20175194)
TANI Kenzaboro  The Inst. of Med. Sci., The Univ. of Tokyo Lecturer, 医科学研究所, 講師 (00183864)
SATO Noriharu  The Inst. of Med. Sci., The Univ. of Tokyo Associate Professor, 医科学研究所, 助教授 (90162461)
OZAWA Keiya  The Inst. of Med. Sci., The Univ. of Tokyo Associate Professor, 医科学研究所, 助教授 (30137707)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥20,000,000 (Direct Cost: ¥20,000,000)
Fiscal Year 1993: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1992: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1991: ¥7,500,000 (Direct Cost: ¥7,500,000)
KeywordsUndifferentiated Leukemia Cell Line / MB-1 / Hematopoietic Factor / Cytokine / Mast cell / Hematopoietic Stem Cell / SCID mouse / cDNA Cloning / cDNAライブラリー / 精製 / ヌードマウス / 白血病細胞株 / SCF / ストローマ細胞 / 慢性骨髄性白血病 / ヌ-ドマウス / 骨髄芽球 / 造血前駆細胞 / ストロ-マ細胞 / 細胞相互作用
Research Abstract

The MB-1 cell line, which was derived from the blastoma of a patient with chronic myelogenous leukemia (CML), is transplantable to nude mice. Mast cell growth-stimulating activity was detected in the culture supernatant of TPA-treated MB-1 cells. Since it is possible that cytokines which stimulate the growth of mast cells have the ability to act on hematopoietic stem cells, it is worth while characterizing the MB-1-derived activity. Although the purification and cDNA cloning of the mast cell growth-stimulating activity of MB-1 cells are still ongoing, our preliminary results suggested that this may be a novel cytokine with a unique activity on mast cells.
We also attempted to establish human leukemia cell lines. The IMS-M1, a monoblastic leukemia cell line with t(9 ; 11) translocation, was established using an in vitro culture system. Unexpectedly, most leukemia samples ware not transplntable to SCID mice, probably due to the absence of appropriate human hematopoietic growth factors.
The other research subjects include malignant transformation of myloid cells using a gene transfer technique and their characterization, molecular cloning of G-CSF-induced gene cDNA, analysis of hematopoiesis-supporting ability of a differentiation-inducible mouse embryo fibroblast cell line (C3H10T1/2), construction of cDNA library derived from human fetal liver, and so forth.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (45 results)

All Other

All Publications (45 results)

  • [Publications] Sato,N.,et al.: "Regulation of mRNA levels of alkaline phosphatase gene in neutrophilic granulocytes by granulocyte colony-stimulating factor and retinoic acid." Eur J Haematol. 46. 107-111 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uemura,N.,et al.: "Acquisition of IL-3-independence in FDC-P2 cells after transfection with the activated c-H-ras gene using a bovine papillomavirus-based plasmid vector." Blood. 80. 3198-3204 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishikawa,M.,et al.: "Deletion mutagenesis of stem cell factor defines the C-terminal sequences essential for its biological activity." Biochem.Biophis.Res.Commun.188. 292-297 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishikawa,M.,et al.: "Changes in hematopoiesis-supporting ability of C3H10T1/2 mouse embryo fibroblasts during differentiation." Blood. 81. 1184-1192 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uemura,N.,et al.: "Binding of membrane-anchored macrophage colony-stimulating factor(M-CSF)to its receptor mediates specific adhesion between stromal cells and M-CSF-receptor-bearing hematopoietic cells." Blood. 88. 2634-2640 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bakic,M.,et al.: "Sustained c-kit expression in a human erythroleukemia cell line(HEL)after megakaryocytic differentiation induced by 12-o-tetradecanoylphorbol-13-acetate(TPA)." Leukemia Res.17. 1079-1082 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fujita,A.,et al.: "Acute myeloid leukemia possibly producing thrombopoietic factor(s)." Biochem.Biophis.Res.Commun.23. 366-372 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimane,M.,et al.: "Molecular cloning and characterization of G-CSF induced gene cDNA." Biochem.Biophis.Res.Commun.199. 26-32 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sato,N.,et al.: "Preferential usage of the bone-type leader sequence for the transcripts of liver/bone/kidny-type alkaline phosphatase gene in neutrophilic granulocytes." Blood. 83. 1093-1101 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi,S.,et al.: "Recombinant human glycosylated granulocyte colony-stimulating factor(rhG-CSF)-combined regimen for a allogeneic bone marrow transplantation in refractory acute myeloid leukemia." Bone Marrow Transplant. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tani,K.,et al.: "Retrovirus-mediated gene transfer of human pyruvate kinase(PK)cDNA into murine hematopoietic cells:Implication for gene therapy of human PK deficiency." Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yoshikubo,T.,et al.: "Adhesion of NFS-60 myeloid leukemia cells to MC3T3-G2/PA6 stromal cells induces G-CSF production." Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Asano,S.: "Hematopoietic Growth Factors-Molecular Biology to Clinical Applications of rG-CSF" Excerpta Medica, (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tani,K.: "Molecular Approaches to the Study and Treatment of Human Diseases." Elsevier Science Publishers B.V., (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ozawa,K.: "Center for Academic Publications Japan" Proceedings of the 1st International Congress on Vitamins and Biofactors in Life Science in Kobe,1991, (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uemura,N.: "The Mechanism and New Approach on Drug Resistance of Cancer Cells." Elsevier Science Publishers B.V., (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sato, N.: "Regulation of mRNA levels of alkaline phosphatase gene in neutrophilic granulocytes by granulocyte colony-stimulating factor and retionoic acid." Eur J Haematol. 46. 107-111 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uemura, N.: "Acquisition of IL-3-independence in FDC-P2 cells after transfection with the activated c-H-ras gene using a bovine papillomavirus plamid vector." Blood. 80. 3198-3204 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishikawa, M.: "Deletion mutagenesis of stem cell factor defines the C-terminal sequences essential for its biological activity" Biochem Biophis. Res. Commun. 188. 292-297 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishikawa, M.: "Changes in hematipoiesis-supporting ability of C3H10T1/2 mouse embryo fibroblasts during differentiation" Blood. 81. 1184-1192 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uemura, N.: "Binding of membrane-anchored macrophage colony-stimulating factor (M-CSF) to its receptor mediates specific adhesion between stromal cells and M-CSF-receptor-bearing hematopoietic cells." Blood. 88. 2634-2640 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bakic, M.: "Sustained c-kit expression in a human erythroleukemia cell line (HEL) after megakaryocytic differentiation induced by 12-o-tetradecanoylphorbol-13-acetate (TPA)." Leukemia Res. 17. 1079-1082 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hujita, A.: "Acute myeloid leukemia possibly thrombopoietic factor(s)." Biochem. Biophis. Res. Commun. 23. 366-372 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimane, M.: "Molecular cloning and characterization of G-CSF induced gene cDNA." Biochem. Biophis. Res. Commun. 199. 26-32 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sato, N.: "Preferential using of the bone-type leader sequence for the transcripts of liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes." Blood. 83. 1093-1101 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi, S.: "Recombinant human glycosylated granulocyte colony-stimulating factor (rhG-CSF)-combined regimen for a allogeneic bone marrow transplantation in refractory acute myeloid leukemia." Bone Marrow Transplant. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tani, K.: "Retrovirus-mediated gene transfer of human pyruvate kinase (PK) cDNA into murine hematopoietic cells : Implication for gene therapy of human PK deficiency" Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yoshikubo, T.: "Adhesion of NFS-60 myeloid leukemia cells to MC3T3-G2/PA6 stromal cells induces G-CSF production" Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Asano, S.: "Hematopoietic Growth Factors-Molecular Biology to Clinical Applications of rhG-CSF" Excerpta Medica. (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tani, K.: "Molecular Approaches to the Study and Treatment of Human Diseases" Elsevier Science. Publishers B.V.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ozawa, K.: "Center for Academic Publications Japan" Proceedings of the 1st International Congress on Vitamins and Biofactors in Life Science in Kobe. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uemura, N.: "The Mechanism and New Approach on Drug Resistance of Cancer Cells." Elsevier Science. Publishers B.V.(1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bakic,M.,Asano,S.,et al.: "Sustained c-Kit expression in a human erythroleukemia cell line(HEL)after megakaryocytic differentiation induced by 12-o-tetradecanoylphorbol-13-acetate(TPA)." Leukemia Res.17. 1079-1082 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shimane,M.,Asano,S.,et al.: "Molecular cloning and characterization of G-CSF induced gene cDNA." Biochem.Biophis.Res.Commun.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Nishikawa,M.,Asano,S.,et al.: "Changes in hematopoiesis-supporting ability of C3H10T1/2 mouse embryo fibroblasts during differentiation." Blood. 81. 1184-1192 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tani,K.,Asano,S.,et al.: "The production of granulocyte colony-stimulating factor and interleukin 6 by human bone marrow stromal cells in aplastic anemia." Tohoku J.Exp.Med.169. 325-334 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Uemura,N.,Asano,S.,et al.: "Binding of membrane-anchored macrophage colony-stimulating factor(M-CSF)to its receptor mediates specific adhesion between stromal cells and M-CSF-receptor-bearing hematopoietic cells." Blood. 88. 2634-2640 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Uemura N. et al.: "Acquisition of interleukin-3 independence in FDC-2 cells after trans fection with the activated c-H-ras gene usirh bovine papillomavirus-based plasmid vector." Blood. 80. 3198-3204 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nishikawa M. et.al.: "Changes in hematopoiesis-supporting ability of C3H1OT1/2mouse embryo fibroblasts during differentiation." Blood. 81. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Kawano et al: "Synergistic effect of recombinant interferon gamma and interleukinー3 on the growth of immature human hematopoietic progenitors." Blood. 77(10). 2118-2121 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S.Asano: "Human GーCSF: Its basic aspects and clinical applications." Am.J.Pediat.Hematol/Oncol.13. 400-417 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Inokuchi et al: "A possible correlation between the type of bcrーabl yhbrid mRNA and platelet count in Philadelphiaーpositive chronic myelogenous leukemia." Blood. 78. 3125-3127 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Tani et al: "Clinical and biological aspects of interferonーalpha in the treatment of chronic myelogenous leukemia." Regulatory Mechanisms of Human Neoplastic Cell Growth by Cytokines:Present and Future Propects.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Tani et al: "Implantation of genetically manipulated fibroblasts into mice as a model of cytokine supplementation gene therapy using human GーCSF and IFNーalpha cDNAs." Molecular Approaches to the Study and Treatment of Human Diseases.

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Ozawa et al: "Hematopoietic Growth Factors/Molecular Biology to Clinical Applications of rhGーCSF" Excerpta Medica, 186 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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