| Project/Area Number |
23659484
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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 |
WATANABE Toshiki 東京大学, 大学院・新領域創成科学研究科, 教授 (30182934)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Kazumi 東京大学, 大学院・新領域創成科学研究科, 助教 (60549591)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | CD4 陽性 T 細胞 / HTLV-1 Tax / Helios / スプライス変異 / ドミナントネガティブ / CD4陽性T細胞 |
|---|
| Research Abstract |
Adult T-cell leukemia is a T-cell neoplasm caused by HTLV-1 infection. In the present study, we found drastic deregulation of Helios expression in ATL cells. Helios is an Ikaros-family transcription factor and a pivotal regulator of T-cell differentiation and activation. Detailed investigations in transcript variants of Helios in PBMCs from ATL patients clarified that the majority of ATL patients demonstrated abnormal splicing patterns of Helios mRNAs, while four cases did not express Helios mRNA at the detectable level. We identified ATL-specific short Helios transcripts and further confirmed that resultant isoforms not only functioned dominant-negatively, but also reduced apoptotic sensitivity and increased proliferation of the cells, probably through activation of S1P pathway, which is deeplyimplicated to cell-motility and proliferation.
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