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Genes that influence the development of adult T-cell leukemia

Research Project

Project/Area Number 10670414
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionEhime University

Principal Investigator

HASEGAWA Hitoshi  Ehime University Hospital, Assistant professor, 医学部・附属病院, 講師 (40164826)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsAdult T-cell leukemia / Tyrosine kinase / Chemokines / CD151 / Adult T-cell leu kemia / Adult T cell leukemia / HTLV-1 / tyrosine Kinase
Research Abstract

The molecular mechanisms that influence the clinical development of adult T cell leukemia (ATL) are not fully understood. In the present study, we tried to identify the mRNA species that are differentially expressed in fresh peripheral blood mononuclear cells from patients with acute ATL and normal subjects, and MOLT-4. The ten genes ; tyrosine kinase Pyk2, JAK3, Tyk, Typo, HYL, Z225, MIP-lalpha, CD151, CCR7/EBI1, and CD70, were amplified preferentially in samples of PBMC from patients with acute ATL.Among these 10 genes, we further analyzed the role of CCR7/EBI1, Pyk2, and CD151 in pathogenesis of ATL.First, ATL cells from patients with lymphoid organ involvement expressed significantly more CCR7/EBI1 than normal T cells and ATL cells from patients without lymphoid organ involvement. This suggests that increased CCR7EBI1 expression plays a role in lymphoid organ infiltration of ATL cells. Second, Pyk2 was expressed higher in 6 freshly isolated ATL cells than in PBMC of normal subjects and MOLT-4. The Pyk2-transfected SF-HT clones grew without IL-2, while control vector-transfected SF-HT cells did not grow. Therefore, these findings suggest that Pyk2 may play a role on the progression of ATL through T cell activation. Finally, the expression levels of CD151, α4β1 integrin, andα5β1 integrin on ATL cells from lymph nodes of lymphoma-type ATL patients were significantly higher than those on circulating ATL cells from leukemia-type ATL patients. This suggests that the increased expression of these integrins may contribute to lymphoma formation.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Hasegawa,H. et al.: "Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells."Blood. 95. 30-38 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa,H. et al.: "CCR7 chemokine receptor expression on normal lymphocyte subsets and adult T-cell leukemia cells."Leucocyto Typing VII,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa,H.and Fujita,S.: "Chemokines and lymphocytes : The role of chemokines and their receptors in the immune system (Review)."Cellular and Molecular Biology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nomura,T.and Hasegawa,H.: "Chemokines and anti-cancer immunotherapy : Anti-tumor effect of EBI1-ligand chemokine(ELC) and secondary lymphoid tissue chemokine(SLC)."Anticancer Research. 20. 4073-4080 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa,H. et al.: "Protein-tyrosine kinase Pyk2 is involved in progression of adult T-cell leukemia."Biochemical and Biophysical Research Communications. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa,H. et al.: "SFA-1/PETA-3 (CD151), a member of the transmembrane 4 superfamily, associates preferentially with alpha5beta1 integrin and regulates adhesion of human T-cell leukemia virus type 1-infected T cells to fibronectin."Journal of Immunology. 161. 3087-3095 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa, H., Nomura, T., Kohno, M., Tateishi, N., Suzuki, Y., Maeda, N., Fujisawa, R., Yoshie, O., and Fujita, S.: "Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells."Blood. 95. 30-38 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa, H., Kohno, M., Nomura, T., Sasaki, M., Yoshie, O., and Fujita, S.: "CCR7 chemokine receptor expression on normal lymphocyte subsets and adult T-cell leukemia cells."7th Workshop and Conference on Human Leucocyte Differentiation Antigens (2000). Abstract : Tissue Antigens. 55. 47 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa, H., Kohno, M., Nomura, T., Sasaki, M., Yoshie, O., and Fujita, S.: "CCR7 chemokine receptor expression on normal lymphocyte subsets and adult T-cell leukemia cells"Leucocyte Typing VII Mason, DY et al. Eds., Oxford University Press. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa, H., and Fujita, S.Chemokines and lymphocytes: "The role of chemokines and their receptors in the immune system (Review)"Cellular and Molecular Biology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nomura, T., and Hasegawa, H.: "Chemokines and anti-cancer immunotherapy : Anti-tumor effect of EBI1-ligand chemokine (ELC) and secondary lymphoid tissue chemokine (SLC)."Anticancer Research. 20. 4073-4080 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa, H., Kohno, M., Nomura, T., Sasaki, M., and Fujita, S.: "Protein-tyrosine kinase Pyk2 is involved in progression of adult T-cell leukemia"Biochemical and Biophysical Research Communications. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa, H., Nomura, T., Kishimoto, K., Yanagisawa, K., and Fujita, S.: "SFA-1/PETA-3 (CD151), a member of the transmembrane 4 superfamily, associates preferentially with alpha5betal integrin and regulates adhesion of human T-cell leukemia virus type 1-infected T cells to fibronectin."Journal of Immunology. 161. 3087-3095 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa,H. et al.: "Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells."Blood. 95. 30-38 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hasegawa,H. et al.: "CCR7 chemokine receptor expression on normal lymphocyte subsets and adult T-cell leukemia cells."Leucocyte Typing VII,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hasegawa,H.and Fujita,S.: "Chemokines and lymphocytes : The role of chemokines and their receptors in the immune system (Review)."Cellular and Molecular Biology,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Nomura,T.and Hasegawa,H.: "Chemokines and anti-cancer immunotherapy : Anti-tumor effect of EBI1-ligand chemokine (ELC) and secondary lymphoid tissue chemokine (SLC)."Anticancer Research. 20. 4073-4080 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hasegawa,H. et al.: "Protein-tyrosine kinase Pyk2 is involved in progression of adult T-cell leukemia."Biochemical and Biophysical Research Communications. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hasegawa,H. et al.: "SFA-1/PETA-3 (CD151), a member of the transmembrane 4 superfamily, associates preferentially with alpha5beta1 integrin and regulates adhesion of human T-cell leukemia virus type 1-infected T cells to fibronectin."Journal of Immunology. 161. 3087-3095 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hasegawa H et al: "Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult the T-cell leukemia cel"Blood. 95. 30-38 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hasegawa H et al: "SFA-1/PETA-3(CD151),a member of the transmembrane 4 superfamily,associates preferentially with α5β1 integrin and regulates adhe"The Journal of Immunology. 161. 3087-3095 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hitoshi Hasegawa.et.al: "SFA-1/PETA-3(CD151),a Member of the Transmembrane4 Superfamily,Associates Preferentially with a5b1 Integrin and Regulates Adhesion of Human T Cell Leukemia Virus Type 1-Infected T Cells to Fibronectin" The Journal of Immunology. 161. 3087-3095 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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