| Project/Area Number |
24390244
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial 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 |
MAEKAWA TAIRA 京都大学, 医学(系)研究科(研究院), 教授 (80229286)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Yasuo 京都大学, 医学研究科, 助教 (70605146)
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| Co-Investigator(Renkei-kenkyūsha) |
HIRAI Hideyo 京都大学, 医学研究科, 助教 (50315933)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
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| Keywords | 白血病幹細胞 / 慢性骨髄性白血病 / 低酸素 / C/EBPβ / 低酸素環境 / 代謝 / 転写因子 / 分子標的治療 |
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| Outline of Final Research Achievements |
Leukemic stem cell hide in hypoxic bone marrow microenvironment and causes therapy resistance and the recurrence. Chronic myelogenous leukemia (CML) stem cells stay in G0 cell-cycle state. CML stem cells alive in such circumstances independent from BCR-ABL expression, so that they are hard to become the target of tyrosine kinase inhibitors (TKI). We found that transcription factor C/EBPβ acted toward differentiation of CML stem cells, and its expression was low in hypoxia. We hypothesized when the expression of C/EBPβ were low, CML stem cells would remain in the G0 state in hypoxia. We found that interferon α (IFN α), independently from BCR-ABL expression, enhanced the expression of C/EBPβ of CML stem cells through STAT5 pathway. In conclusion, IFN α could drive CML stem cells into cell-cycle state by enhancing their expression of C/EBPβ and differentiate them. These differentiated from CML stem cells proliferate in BCR-ABL dependent fashion, and could become the target of TKI.
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