2012 Fiscal Year Final Research Report
Regulation of leukemia stem cells in MOZ-TIF2 AML
| Project/Area Number |
23791206
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
SHIMA Haruko 独立行政法人国立がん研究センター, 研究所, 特任研究員 (80424167)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 白血病幹細胞 / MOZ-TIF2 |
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| Research Abstract |
This study was performed to determine the characteristics of MOZ-TIF2 AML stem cells using two different assay systems. Firstly, we showed that BRPF1/HOX pathway is critical for the leukemogenesis by MOZ-TIF. Our data indicate that BRPF1 recognizes histone modifications and stimulates MOZ localization on target genes, and upregulates transcription of target genes such as HoxA9 and Hoxa10, which finally promotes development of leukemia. Secondary, we focused on Ring1A and Ring1B, the components of PRC1 complex, which plays an important role in the regulation of stem cells. We found that Ring 1A/B play crucial roles in the maintenance of MOZ-TIF2 leukemia through repression of Glis2, which strongly promotes differentiation of leukemia stem cells.
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