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Molecular control of the regulation of hemopoiesis and clinical application

Research Project

Project/Area Number 07407029
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research Institutionjichi Medical School

Principal Investigator

MIURA Yasusada  Jichi Medical School, Professor, 医学部, 教授 (60048965)

Co-Investigator(Kenkyū-buntansha) MUROI Kazuo  Jichi Medical School, Assistant Professor, 医学部, 講師 (50190939)
IMAGAWA Shigehiko  Jichi Medical School, Assistant Professor, 医学部, 講師 (60231164)
TAKATOKU Masaaki  Jichi Medical School, Assistant, 医学部, 助手 (20285787)
HATAKE Kiyohiko  Jichi Medical School, Associate Professor, 医学部, 助教授 (80192699)
KOMATSU Norio  Jichi Medical School, Assistant Professor, 医学部, 講師 (50186798)
清水 律子  自治医科大学, 医学部, 助手 (40226262)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥33,800,000 (Direct Cost: ¥33,800,000)
Fiscal Year 1997: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1996: ¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1995: ¥20,700,000 (Direct Cost: ¥20,700,000)
Keywordshemopoietic stem cell / hemopoietic factor / erythropoietin gene / megakaryocytic cell line / transcription factor / erythropoietin receptor / hemopoietic stem cell disorders / apoptosis / GATA-1 / 赤白血病
Research Abstract

Molecular control of the regulation of hemopoiesis and clinical application
1.We investigated molecular control of the regulation of hemopoiesis using a megakaryocytic cell line UT-7 and its sublines.
After culturing long time with GM-CSF,we established an immature blastic subline UT-7/GM.This cell line differentiates into erythroid lineage by the addition of erythropoietin (EPO), and into megakaryocytic lineage by thrombopoietin (TPO). GM-
CSF suppresses its differentiation. Transcription factors STAT 1alpha, 3 and 5 were activated by GM-CSF and TPO,while only STAT1alpha was activated by EPO.The detailed mechanism was investigated using transfetants of STAT molecules.
2.By the continuous addition of TPO,we established a TPO-dependent sub-cell line, which expresses megakaryocytic feature, and characterized its signal pathway following the addition of TPO.
3.We reported that regulation of EPO receptor gene is cycle dependent, by using UT-7 cell line.
4.Disialosyl-T antigen was found to be involved in the erythroid differentiation.
5.GATA sequence at 5'promotor region of EPO gene was found to suppress the expression of EPO gene
6.Role of apoptosis-related genes, Fas bcl-x etc was investigated.
7.7.We could not find any mutation in a patient with congenital megakaryopenic thrombocytopenia. In this concern, primitive cd34+stem cells express TPO receptor K.After differentiation by culturing with TPO,they express P type receptors. This may shed a light on the role of K type receptor.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Kikuchi, J., et al: "Polyploidization and functional maturation are two distinct processes during megakaryocytic differentiation." Blood. 89. 3980-3990 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Imagawa, S., et al: "Negatve regulation of the erythropoietin gene expression by the GATA transcription factors." Blood. 89. 1430-1439 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Komatsu, N., et al: "Cell-cycle dependent regulation of erythropoietin receptor gene." Blood. 89. 1182-1188 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Komatsu, N., et al: "Invitro development of erythroid and megakaryocytic cells from a UT-7 subline, UT-7/GM." Blood. 89. 4021-4033 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takatoku, M., et al: "Identification of functional domains of the human thrombopoietin signal transduction." J.Biol.Chem.272. 7259-7263 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kirito, K., et al: "A novel function of Stat1a and Stat3 proteins in erythropoietininduced erythroid differentiation of a human leukemia cell line." Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Komatsu, N., Kunitama, M., Yamada., Hagiwara, T., Kato, T., Miyazaki, H., Eguchi, M., Yamamoto, M., Miura, Y.: "Establishment and characterization of the thrombopoietin-dependent megakaryocytic cell line, UT-7/TPO." Blood. 87. 4552-4560 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takatoku, M., Kametaka, M., Shimizu, R., Miura, Y., Komatsu, N.: "Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation.of megakaryocytic cells." J.Biol.Chem.272. 7259-7263 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Komatsu, N., Kirito, K., Kashii, Y., Furukawa, Y., Kikuchi, J., Suwabe, N., Yamamoto, M., Miura, Y.: "Cell-cycle dependent regulation of erythropoietin receptor gene." Blood. 89. 1182-1188 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Imagawa, S., Yamamoto, M., Miura, Y.: "Negative regulation of the erythropoietin gene expression by the GATA transcription factors." Blood. 89. 1430-1439 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Komatsu, N., Kirito, K.m, Shimizu, R., Kunitama, M., Yamada, M., Uchida, M., Takatoku, M., Eguchi, M., Miura, Y.: "In vitro development of erythroid and megakatyocytic cells from a UT-7 subline, UT-7/GM." Blood. 89. 4021-4033 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kirito, K., Uchida, M., Yamada, M., Miura, Y., Komatsu, N.: "A distinct function of STAT proteins in erythropoietin signal transduction." J.Biol.Chem.272. 16507-16513 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miura Yasusada: "Kekkyu sansei chosetsu no bunshi kiko to rinsho" Nichinaikai-shi. 85. 1420-1430 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kikuchi,J., Furukawa,Y., Iwase,S., Miura,Y., et al.: "Polyploidization and functional maturation are two distinct processes during meqakaryocytic differentiation." Blood. 89. 3980-3990 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Imagawa,S., Yamamoto,M., Miura,Y.: "Negative requlation of the erythropoietin gene expression by the GATA transcription factors." Blood. 89. 1430-1439 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Komatsu,N., Kirito,K., Kashii,Y., Miura,Y., et al.: "Cell-cycle dependent requlation of erythropoientin receptor gene." Blood. 89. 1182-1188 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Komatsu,N., Kirito,K., Shimizu,R., Miura,Y., et al.: "In vitro development of reythroid and megakaryoeytic cells from a UT-7 subline,UT-7/GM." Blood. 89. 4021-4033 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kunitama,M., Shimizu,R., Miura,Y., Komatsu,N., et al.: "Protein kinase C and c-myc gene activation pathways in thrambopoietin signal transduction." Biochem.Biophys.Res.Commun.231. 290-294 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takatoku,M., Kametaka,M., Miura,Y., Komatsu,N., et al.: "Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells." J.Biol.Chem.272. 7259-7263 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohtsuki,T.,Hatake,K.,Ikeda,M.,Miura,Y.,et al.: "Binding of macrophage colony-stimulating factor to serum proteins" Experimental Hematology. 24. 101-107 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shimizu,R.,Komatsu,N.,Nakamura,Y.,Miura,Y.,et al.: "Role of c-jun in the inhibition of erythroietin receptor mediated apoptosis." Biochem.Biophysic.Res.Commun.222. 1-6 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Komatsu,N.,Kunitama,M.,Yamada,M.,Miura,Y.,et al.: "Establishment and characterization of the thrombopoietin-dependent megakaryocytic cell line,UT-TPO." Blood. 87. 4552-4560 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Komatsu,N.,Kirito,K.,Kashii,Y.,Miura,Y.,et al.: "Cell-cycle dependent regulation of erythropoietin receptor gene." Blood. 89. 1182-1188 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Imagawa,S.,Yamamoto,M.,Miura,Y.: "Negative regulation of the erythropoietin gene expression by the GATA transcription factors." Blood. 89. 1430-1439 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takatoku,M.,Kametaka,M.,Shimizu,R.,Miura,Y.: "Identification of functional domains of human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells." J.Biol.Chem.(in press)(3月刊予定). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Imagawa,S.,Yamamoto,M.,Miura,Y.: "Molecular Biology of Hematopoiesis" GATA transcription factors negatively regulate erythropoietin gene expression., 13 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] k. Muroi, M. Nakamura Y. Miura, et al.: "Expression of c-kit receptor (CD17) and CD34 in leukemic cells" Leukemia and Lymphoma. 16. 297-305 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Suzuki, T., Miura, Y. et al.: "Characterization of enriched CD34 cells from healthy voluntears and those from patients treated with chemotherapy granulacyte colony-stimulating factor (G-CSF)" Stem Cells. 13. 273-280 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hoshino, Y., Miura, Y., et al.: "Monocyte chemoattractant protein-1 stimulates tumor necrosis and recruitment of macrophages into tumors in tumor- bearing nude mice : Increased granulocyte and macrophage progenitors in murine bone marrow." Experimental Hematology. 23. 1035-1039 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ohtsuki, T., Miura, Y., et al.: "Immunohistochemical identification of proteoglycan form of macrophage colony-stimulating factor on bone surface." Calcif Tissue Int.57. 213-217 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamada, M., Miura, Y., et al.: "Thrombopoietin induces tyrosin phosphorylation and activattion of mitogen-activated protein kinase in a human thrombopoietin-dependent cell line." Biochemical Biophysical Research Communications. 217. 230-237 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Komatsu, N., Miura, Y.: "Establishment and characterization of the thrombopoietin-dependent megakaryocytic cell line, UT-7/TPO" Blood. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Tomizuka, H., Miura, Y., et al.: "Myelodysplastic Syndromes : Advances in Research and Treatment" Elsevier Science B. V., 11 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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