| Project/Area Number |
25430149
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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 |
Tumor therapeutics
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| Research Institution | Kyoto University |
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Principal Investigator |
Yokota Asumi 京都大学, 医学(系)研究科(研究院), 研究員 (00571556)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAI Hideyo 京都大学, 医学研究科, 助教 (50315933)
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| Co-Investigator(Renkei-kenkyūsha) |
MAEKAWA Taira 京都大学, 医学研究科, 教授 (80229286)
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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 |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 転写因子 / 慢性骨髄性白血病 / 白血病幹細胞 / サイトカイン |
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| Outline of Final Research Achievements |
By analysis using a next-generation sequencer, we identified a novel 3’ distal enhancer region of Cebpb, where STAT5 are recruited in a BCR-ABL signaling-dependent manner.
We also found that IFNα, which has been used for the treatment of CML, can efficiently upregulate C/EBPβ expression, and promote exhaustion and differentiation of CML stem cells through C/EBPβ. Interestingly, IFNα phosphorylate STAT5 including STAT1 and STAT3, and recruited STAT5 to a Cebpb enhancer region, which we identified in this study. IFNα also decreased CML stem cells in a mouse model, and this effect is abolished in C/EBPβ-deficient CML stem cells, indicating that the in vivo effect of IFNα is mediated by C/EBPβ.
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