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2003 Fiscal Year Final Research Report Summary

Elucidation of signal transduction pathway via HM1.24 and application toward the treatment of hematological malignancies

Research Project

Project/Area Number 14570984
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionThe University of Tokushima

Principal Investigator

OZAKI Shuji  University of Tokushima, University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (90314872)

Co-Investigator(Kenkyū-buntansha) ABE Masahiro  University of Tokushima, University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (80263812)
SHIBATA Hironobu  University of Tokushima, University Hospital, Medical Staff, 医学部・歯学部附属病院, 医員
Project Period (FY) 2002 – 2003
Keywordshematological malignancy / immnnotherapy / molecular targeting therapy
Research Abstract

We first identified the cDNA for human HM1.24 antigen and also analyzed its gene structure including the promoter region. The HM1.24 antigen was an identical molecule that has been reported as a bone marrow stromal cell surface antigen 2. Interestingly, the promoter region of the HM1.24 gene has a tandem repeat of three cis elements for transcription factors such as ISRE, GAS, and STAT3. In fact, stimulation with interferon induced the expression of HM1.24 antigen in hematological malignant cells. We next investigated the mechanism of cell death induced by HM1.24 antibody. The HM1.24 antibody induced cell aggregation in neoplastic cells in the presence of secondary antibody. These cells were positive for annexin V and TUNEL staining, suggesting the induction of apoptosis. Next, we examined the effects of HM1.24 antibody in combination with chemotherapy drugs. Cell growth of myeloma cells was inhibited by melphalan or etoposide in a dose-dependent manner, and was further suppressed by HM1.24 antibody together with secondary antibody. Treatment with interferon up-regulated the expression of HM1.24 in leukemic cells, and enhanced cell death of leukemic cells by HM1.24 antibody. In addition, to establish cell immunotherapy targeting HM1.24, we attempted to generate cytotoxic T lymphocytes specific for HM1.24. After stimulation with dendritic cells pulsed with HM1.24-derived peptides, HM1.24-specific cytotoxic T lymphocytes were successfully induced from peripheral T cells. These findings suggest that HM1.24 is a potential target for immunotherapy in patients with hematological malignancies.

  • Research Products

    (12 results)

All 2004 2002

All Journal Article (12 results)

  • [Journal Article] Primary adult T-cell leukemia/lymphoma of bone2004

    • Author(s)
      Hara T
    • Journal Title

      Int J Hematol 79

      Pages: 157-160

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Aggressive natural killer-cell leukemia revisited : large granular lymphocyte leukemia of cytotoxic NK cells2004

    • Author(s)
      Suzuki R
    • Journal Title

      Leukemia 18

      Pages: 763-770

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ability of myeloma cells to secrete macrophage inflammatory protein(MIP)-1a and MIP-1 b correlates with lytic bone lesions in patients with multiple myeloma2004

    • Author(s)
      Hashimoto T
    • Journal Title

      Br J Haematol 125

      Pages: 38-41

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Osteoclasts enhance myeloma cell growth and survival via cell-cell contact : a vicious cycle between bone destruction and myeloma expansion2004

    • Author(s)
      Abe M
    • Journal Title

      Blood 104

      Pages: 2484-2491

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 2D7 diabody bound to the α2 domain of HLA class I efficiently induces caspase-independent cell death against malignant and activated lymphoid cells2004

    • Author(s)
      Kimura N
    • Journal Title

      Biochem Biophys Res Commun 325

      Pages: 1201-1209

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Primary adult T-cell leukemia/lymphoma of bone2004

    • Author(s)
      Hara T, et al.
    • Journal Title

      Int J Hematol 79

      Pages: 157-160

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Aggressive natural killer-cell leukemia revisited : large granular lymphocyte leukemia of cytotoxic NK cells2004

    • Author(s)
      Suzuki R, et al.
    • Journal Title

      Leukemia 18

      Pages: 763-770

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)-1a and MIP-1 b correlates with lytic bone lesions in patients with multiple myeloma2004

    • Author(s)
      Hashimoto T, et al.
    • Journal Title

      Br J Haematol 125

      Pages: 38-41

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Osteoclasts enhance myeloma cell growth and survival via cell-cell contact : a vicious cycle between bone destruction and myeloma expansion2004

    • Author(s)
      Abe M, et al.
    • Journal Title

      Blood 104

      Pages: 2484-2491

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 2D7 diabody bound to the alpha2 domain of HLA class I efficiently inducescaspase-independent cell death against malignant and activated lymphoid cells2004

    • Author(s)
      Kimura N, et al.
    • Journal Title

      Biochem Biophys Res Commun 325

      Pages: 1201-1209

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role for macrophage inflammatory protein(MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma2002

    • Author(s)
      Abe M
    • Journal Title

      Blood 100

      Pages: 2195-2202

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma2002

    • Author(s)
      Abe M, et al.
    • Journal Title

      Blood 100

      Pages: 2195-2202

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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