| Project/Area Number |
22591162
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 |
EGUCHI Mariko 愛媛大学, 大学院・医学系研究科, 准教授 (40420781)
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| Co-Investigator(Kenkyū-buntansha) |
EGUCHI Minenari 愛媛大学, 医学部附属病院, 講師 (50420782)
ISHII Eichi 愛媛大学, 大学院・医学系研究科, 教授 (20176126)
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| Co-Investigator(Renkei-kenkyūsha) |
NAKAHATA Tatsutoshi 京都大学, iPS 細胞研究センター, 教授 (20110744)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 小児腫瘍学 / MLL / ES細胞 / 造血細胞分化 / 白血病 |
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| Research Abstract |
To study the developmental impact of MLL-AF4 fusion gene on early hematopoietic development, mouse embryonic stem (ES) cells with constitutive expression of MLL-AF4 were established. When hematopoietic differentiation was examined by embryoid body (EB) formation, Tie2^+c-kit^+cells which contain early hematopoietic stem cells were significantly reduced in MLL-AF4 expressing Ebs compared to that of control Ebs.Expression array analysis indicated that MLL-AF4 works as positive regulator of gene expression up-regulating various genes. Several genes up-regulated by MLL-AF4 were known to have important roles in cell differentiation to mesenchymal lineage, whereas transcriptional regulator of hematopoietic lineage were down-regulated. These MLL-AF4 expressing pre-hematopoietic stem cells with mesenchymal nature, were unable to cause leukemia in vitroor in vivo, showing that some secondary event is necessary to cause leukemia. MLL-AF4, having the potential to influence early hematopoietic cell differentiation, may cause leukemic transformation whenaccompanied by some important additional genetic events.
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