| Project/Area Number |
16K15500
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kurokawa Mineo 東京大学, 医学部附属病院, 教授 (80312320)
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| Project Period (FY) |
2016-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | epigenetics / Runx1 / Nras G12D / エピジェネティクス / 白血病 |
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| Outline of Final Research Achievements |
We introduced NRasG12D mutation to hematopoietic stem cells (HSCs) from Runx1 conditional null mice and tried to shut off the expression of mutant NRas after developing acute myeloid leukemia (AML) to compare epigenetic status of leukemia stem cells before and after NRas silencing. Our goal was to elucidate an essential epigenetic mechanism for pathogenesis of AML. We lentivirally transduced NRasG12D into Runx1 flox/flox HSCs with various multiplicity of infection to titrate the expression levels, followed by transplantation into lethally irradiated recipient mice. After four-month observation period, they didn’t develop AML, possibly due to cytotoxicity by lentivirus and low expression levels of ectopic NRas G12D. Now we are developing new inducible AML models using retroviral gene transduction and other gene abnormalities.
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