| Project/Area Number |
17K10115
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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 |
Pediatrics
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| Research Institution | Ehime University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石井 榮一 愛媛大学, 医学系研究科, 教授 (20176126)
江口 真理子 愛媛大学, 医学系研究科, 教授 (40420781)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 小児白血病 / 白血病幹細胞 / 前白血病幹細胞 / MLL-AF4融合遺伝子 / TEL-AML1融合遺伝子 / MLL融合遺伝子 / TEL融合遺伝子 / 小児血液学 / 白血病 |
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| Outline of Final Research Achievements |
MLL-AF4 and TEL-AML1 fusion genes are frequently observed in childhood acute lymphocytic leukemia (ALL). Leukemogenic process with these fusion genes were analyzed in vitro and in vivo with mouse embryonic stem (ES) cell expressing MLL-AF4 or TEL-AML1 fusion and immunodeficient mice (NOG mice) transplanted with fusion gene-expressing ES cell-derived immature hematopoietic cells. It was shown that the presence of these leukemia-specific fusion genes alone was not sufficient for leukemic transformation and hematopoietic progenitors with MLL-AF4 or TEL-AML1 fusion still remained at the stage of pre-leukemic stem cell without full transformation activity to cause leukemia rapidly in immunodeficient mice. These pre-leukemic stem cells could progress to leukemic stem cell after introducing random insertional mutations by retroviral integration indicating that some additional genetic abnormalities may be essential for the final progression to leukemic stem cells and leukemic transformation.
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| Academic Significance and Societal Importance of the Research Achievements |
白血病における前白血病幹細胞の存在は以前から示唆されてきたが、小児白血病における詳細な研究は少ない。前白血病幹細胞は多様な白血病幹細胞を生み出す発生母地となり、白血病再発・治療抵抗性の原因となり得る細胞であるが、現在まで治療対象としての研究もなされていない。白血病の再発の連鎖を断ち切るためには前白血病幹細胞の根絶が必須であり、その生存・維持のメカニズムと白血病幹細胞への進展のメカニズムが明らかになれば、新たな分子標的療法の開発へつながり、小児のみならず、成人領域の白血病患者の予後改善が可能となる。
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