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Development of the method to surmise the prognosis of acute myeloblastic leukemia patients by analyzing the expression of Notch protein

Research Project

Project/Area Number 13672415
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TOHDA Shuji  Tokyo Medical and Dental University, Department of Laboratory Medicine, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80251510)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsacute myeloblastic leukemia / Notch / Jagged / Delta / 白血病
Research Abstract

The self-renewal and differentiation of hematopoietic progenitors are regulated by the interaction between Notch receptors and Notch ligands. Since acute myeloblastic leukemia (AML) originates from dysregulated hematopoietic progenitors, we thought that some abnormalities in the Notch system might be involved in the abnormal proliferation of AML cells. Furthermore, we thought that the expression of Notch protein might be one of the prognostic factors of the patients. Firstly, we found that most of the AML cell lines and half of the primary AML cells from patients expressed Notch-1 protein. Some samples showed a fragment which appeared to be a constitutively active form or an aberrant sized fragment. Other samples expressed the Notch ligand protein such as Jagged 1. Secondly, we established a novel human AML cell line, TMD7, of which growth was stimulated by Notch ligands. Thirdly, we examined the effects of recombinant Notch ligand proteins on in vitro growth of AML cells. For TMD7 cells, the Notch ligand promoted the short-term growth, however, suppressed the self-renewal capacity and long-term growth. For another cell line, Notch ligand protein suppressed the growth and self-renewal capacity while inducing differentiation into macrophage-like cells. We additionally found that Notch ligands needed to be immobilized on culture wells to affect the cells. At present, we are examining the effects of the Notch ligands on the growth of primary AML cells from patients. Until now, we have not found the clear relationship between the prognosis of the patients and the expression of Notch proteins.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Tohda S: "Expression of Notch I and jagged I proteins in acutemyeloid leukemia cells"Leukemia and Lymphoma. 42・3. 467-472 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohda S: "Human herpesvirus 8 DNA in HIV-negative Japanese patients with multicentric Casfleman's disease and related diseases"International Journal of Molecular Medicine. 8. 549-551 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohda S: "A novel cell line derived from de novo acute myeloblastic leukaemia with trilineage myelodysplasia which proliferates in response to a Notch ligand, Delta-1 protein"British Journal of Haematology. 117. 373-378 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohda S: "Notch ligands, Delta-1 and Delta-4 suppress the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines"International Journal of Oncology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohda S, Nara N: "Expression of Notch 1 and Jagged 1 proteins in acute myeloid leukemia cells"Leukemia and Lymphoma. 42. 467-472 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohda S, Murakami N, Nara N: "Human herpesvirus 8 DNA in HIV-negative Japanese patients with multicentric Castleman's disease and related diseases"International Journal of Molecular Medicine. 8. 549-551 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohda S, Sakano S, Ohsawa M, Murakami N, Nara N: "A novel cell line derived from de novo acute myeloblastic leukaemia with trilineage myelodysplasia which proliferates in response to a Notch ligand, Delta-1 protein"Brltish Journal of Haematology. 117. 373-378 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohda S, Murata-Ohsawa M, Sakano S, Nara N: "Notch ligands, Delta-1 and Delta-4 suppress the self-renewal capacity and long term growth of two myeloblastic leukemia cell lines"lnternational Journal of Oncology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohda S: "Expression of Notch 1 and Jagged 1 proteins in acute myeloid lenkemia cells"Lenkemia and Lymphoma. 42・3. 467-472 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tohda S: "Human herpes virus 8 DNA in HIV-negative Japanese patients with multicentrit Castlemun's disease and related diseases"International Journal of Molecular Medicine. 8. 549-551 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tohda S: "A novel cell line derived from de novo acute myeloblastic lenkaemia with trilineage myelodysplasia which proliferates in response to a Notch ligand, Pelto-1 protein"British Journal of Haematulogy. 117. 373-378 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tohda S: "Notch ligands, Delta-1 and Delta-4 suppress the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines"International Journal of Oncology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Tohada S: "Expression of Notch 1 and 1 protein in acute myeloid leukemia cells"Lenkemia and Lymphoma. 42・3. 467-472 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tohda S: "A novel cell line derived from de nove acute myelohlastic Leukaemia with trilineage myelodysphasid which prolifevates in response to a Notch ligand, Delta 1 protein"British Journal of Haematology. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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