| Project/Area Number |
19K17829
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Jun Toda 大阪大学, 医学部附属病院, 医員 (90770834)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 慢性骨髄性白血病 / 白血病幹細胞 / STAP-1 / アダプター蛋白 / CML / CML幹細胞 / STAP蛋白 / BCR-ABL / STAP |
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| Outline of Research at the Start |
本研究では、STAP-1またはSTAP-2 KOマウスにて作製したCMLモデルにおいて、STAP蛋白ファミリーがCMLの病勢進行と幹細胞へ与える影響を検討し、その機構について明らかにする。Gene expression profilingを行うことで、特にCML幹細胞におけるBcr-Abl依存性・非依存性経路でのSTAP蛋白の作用メカニズムを詳細に解析する予定である。
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| Outline of Final Research Achievements |
First, I found that STAP-1 expression was up-regulated in human CML stem cells compared to normal stem cells.
Next, we conducted experiments in mice. Analysis of STAP-1 deficient CML mice revealed a significant decrease in the number of CML stem cells, and annexin staining revealed enhanced apoptosis in STAP-1 deficient CML stem cells, suggesting that STAP-1 contributes to survival by inhibiting apoptosis in CML stem cells.
We also performed RNA sequencing using CML stem cells and found that STAP-1 is involved in the phosphorylation of STAT5, which in turn regulates the expression of anti-apoptotic factors such as Bcl-2 and Bcl-xl. These data indicate that STAP-1 is an important molecule for the maintenance of CML stem cells. In this study, STAP-1-mediated signaling was newly identified as one of the therapeutic targets for stem cell targeting.
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| Academic Significance and Societal Importance of the Research Achievements |
今回のSTAP-1を介したシグナル伝達の解明はCML幹細胞をターゲットとした治療の開発において、大きな意義があると考えられた。また、STAP-1そのものも、正常造血への影響が少ないと考えられるため、副作用の少ない、新たな治療標的として用いられることが期待される。
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