| Project/Area Number |
25461415
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto University |
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Principal Investigator |
Hirai Hideyo 京都大学, 医学(系)研究科(研究院), 助教 (50315933)
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| Co-Investigator(Renkei-kenkyūsha) |
MINAMISHIMA Yoji 慶應義塾大学, 医学部, 講師 (20593966)
MAEKAWA Taira 京都大学, 医学研究科, 教授 (80229286)
YOKOTA Asumi 京都大学, 医学研究科, 研究員 (00571556)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 白血病幹細胞 / 低酸素 / 転写因子 / 慢性骨髄性白血病 / C/EBPbeta / サイトカイン / 骨髄微小環境 |
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| Outline of Final Research Achievements |
In order to achieve complete cure of chronic myeloid leukemia (CML), eradication of CML stem cells (CML-SCs) is cruicial.
In this study, we focused on hypoxic microenvironment and regulation of the transcription factor C/EBPbeta, which is activated by BCR-ABL and promotes differentiation and exhaustion of CML-SCs. Hypoxic condition in vitro reduced the expression of C/EBPbeta in CML cell lines, and cytokine treatment could not reverse this effect. In contrast, when the mice, which had been transplanted with BCA-ABL expressing bone marrow cells, were treated with cytokines, exhaustion of CML-SCs were promoted via upregulation of C/EBPbeta. These results suggest that cytokine treatment may eradicate CML-SCs by remodeling bone marrow microenvironment including hypoxia in addition to direct action on CML-SCs.
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