Mechanisms of chromosomal translocations through the epigenetic regulation.
| Project/Area Number |
25860794
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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 |
Hematology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
WADA Taeko 自治医科大学, 医学部, 助教 (30382956)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 前白血病幹細胞 / エピジェネティクス / T細胞性リンパ芽急性白血病 / ヒストン脱メチル化酵素 / 前白血病状態 / 造血幹細胞 / T細胞性リンパ芽球性白血病 |
|---|
| Outline of Final Research Achievements |
We demonstrate that LSD1 overexpression is a founder abnormality for the development of T-cell lymphoblastic leukemia/lymphoma (T-LBL). Overexpression of the shortest isoform of LSD1, which is selectively repressed in quiescent HSCs and demethylates histone H3K9 more efficiently than other isoforms, increases self-renewal potential via up-regulation of the HoxA family, but retains the multi-differentiation ability with a skewed differentiation to T-cell lineages at transcriptome levels in HSCs. Transgenic mice overexpressing LSD1 in HSCs did not show obvious abnormalities but developed T-LBL at very high frequency after irradiation.LSD1 overexpression appears to be the first hit in T-cell leukemogenesis and provides an insight into novel strategies for early diagnosis and effective treatment of the disease.
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Report
(3 results)
Research Products
(4 results)
