Elucidation of signal transduction pathway via HM1.24 and application toward the treatment of hematological malignancies
| Project/Area Number |
14570984
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
OZAKI Shuji University of Tokushima, University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (90314872)
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| 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
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | hematological malignancy / immnnotherapy / molecular targeting therapy / 造血器腫瘍 |
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| 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.
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Report
(3 results)
Research Products
(22 results)
