| Project/Area Number |
15591096
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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 |
Pediatrics
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| Research Institution | University of Yamanashi |
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Principal Investigator |
GOI Kumiko University of Yamanashi Hospital, Research associate, 医学部附属病院, 助手 (70324192)
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| Co-Investigator(Kenkyū-buntansha) |
SUGITA Kanji University of Yamanashi Hospital, Lecturer, 医学部附属病院, 講師 (60138055)
INUKAI Takeshi University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Research associate, 大学院・医学工学総合研究部, 助手 (30293450)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | acute lymphoblastic leukemia / Histone deacetylase inhibitor / apoptosis / cell cycle arrest / differentiation / 脱メチル化剤 / 分化誘導 / HDAC inhibitor / apoptosis |
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| Research Abstract |
Inhibitors of histone deacetylase (HDAC) have been shown to induce both apoptosis and cell cycle arrest in various tumor cells. Although there are several reports on the effect of HDAC inhibitors on myeloid and T-cell leukemia, few studies have performed on B-precursor acute lymphoblastic leukemia (ALL). In the present study, we extensively examined the biological effects of trichostatin A (TSA), a representative HDAC inhibitor, on B-precursor cell lines (11q23 translocation, Philadelphia chromosome, and others) and T-cell cell lines, and showed that both B-precursor and T-cell, but not myeloid, lines were very sensitive to TSA in both induction of apoptosis and cell cycle arrest. TSA with demethylating agent 5'aza also induced monocytic differentiation in 11q23 cell line, The apoptosis pathway was caspase-dependent and Western blot analysis revealed upregulation of Bak and downregulation of Bcl-XL. B-precursor cell lines showed G1 arrest accompanied by the p53-independent p21 upregulation with or without a decrease in the CDK4 expression, whereas T-cell lines showed G2 arrest accompanied by the CyclinB downregulation. TSA treatment also strongly induced downregulation of c-Myc in all of the B-precursor and T-cell lines. TSA might have a therapeutic potential for the treatment of these malignancies.
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