Functional analysis of STAP family proteins in CML

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17829
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Osaka University
• Principal Investigator: Jun Toda 大阪大学, 医学部附属病院, 医員 (90770834)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 慢性骨髄性白血病 / 白血病幹細胞 / STAP-1 / アダプター蛋白

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.

Free Research Field

白血病

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。