| Project/Area Number |
17K19599
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Hiroshima University |
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Principal Investigator |
NAKA KAZUHITO 広島大学, 原爆放射線医科学研究所, 准教授 (70372688)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | ジペプチド / がん幹細胞 / 抗がん剤抵抗性 / オンコ ニュートリエント / メタボローム / トランスポーター / 再生医療 / トランスポータ / 再発治療 / オンコ ニュートリエント / 代謝 |
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| Outline of Final Research Achievements |
Although the discovery of tyrosine kinase inhibitors (TKIs) has been improved prognosis of chronic myelogenous leukemia (CML) patients, CML stem cells are responsible for the relapse of CML disease following TKI therapy. We have previously reported that internalization of dipeptide species plays a crucial role for surviving CML stem cells in vivo. In this study, we examined a biological role of dipeptide species in the maintenance of CML stem cells by using Slc15A2-deficient CML mouse model, which cannot take up dipeptide species. Interestingly, RNA-sequencing study indicated that the defective dipeptide internalization induced differentiation of CML stem cells to granulocyte macrophage progenitor (GMP)-like CML cells. Therefore, our results suggested that inhibiting dipeptide uptake contributes to development of new differentiation therapy to eradicate CML stem cells in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
がん幹細胞はがん細胞を産み出す能力と抗がん剤抵抗性を併せ持つ細胞であり，抗がん剤治療を逃れたがん幹細胞は再発を引き起す原因となる．研究代表者は，CML幹細胞はジペプチドを吸収して生存していることを報告したが，その生物学的意義は不明であった．本研究では，ジペプチド吸収できないSlc15A2遺伝子のノックアウトマウスを用いることで，ジペプチドの吸収は生体内でのCML幹細胞の未分化性の維持に重要な役割を担うことを解明した．本成果はSlc15A2阻害剤による分化誘導など，CML幹細胞を標的とする新しいCML根治療法を開発するための医薬基盤となることが期待される．
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