| Project/Area Number |
16K14635
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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 |
Tumor therapeutics
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| Research Institution | Tokai University |
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Principal Investigator |
ANDO Kiyoshi 東海大学, 医学部, 教授 (70176014)
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| Co-Investigator(Kenkyū-buntansha) |
八幡 崇 東海大学, 医学部, 准教授 (10398753)
穂積 勝人 東海大学, 医学部, 教授 (30246079)
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| Co-Investigator(Renkei-kenkyūsha) |
HIRAYAMA Noriaki 東海大学, 先進生命科学研究所, 教授 (70238393)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Notch / 血液腫瘍 / T-ALL / Lmo2 / 抗腫瘍薬 / LMO2 / 悪性腫瘍 / 急性リンパ球性白血病 / 創薬 |
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| Outline of Final Research Achievements |
It was known that more than 50% of human T-ALL have activating mutations that generate constitutive active form of of NOTCH1. However, the gamma-secretase inhibitors (restrain the proteolysis of Notch receptor) have never been widely administrated because of their toxicity. We show that Lmo2, frequently expressed in hematopoietic stem cells and a high-risk subtype of T-ALL with stem cell-like features (ETP-ALL), contributes to the maintenance of their differentiation potential toward T cell lineage and its repression induces their cell death with Notch signaling. Lmo2 is adaptor protein in transcriptional complex and preserve cell viability via Bcl11a and Bcl2. Moreover, the reduction of Lmo2 in originally established murine ETP-ALL-like cells also leads growth arrest. These results raise the possibility that Lmo2 is a potent target of newly identified drug for ETP-ALL.
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