| Project/Area Number |
21591222
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SUZUKI Hiroshi 東京大学, 大学院・医学系研究科, 特任助教 (00587793)
FUJIMURA Tsutomu 順天堂大学, 医学系, 准教授 (70245778)
TAKAGI Masatoshi 東京医科歯科大学, 医歯学総合研究科, 講師 (10406267)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | L-asparaginase / NK細胞リンパ腫 / eIF4E / グルタミン / TCAサイクル / NK細胞腫瘍 / alpha-ケトグルタル酸 / アポトーシス / 癌細胞代謝 / 炭素骨格分子 / 翻訳開始因子群 / MYC |
|---|
| Research Abstract |
We have shown two new mechanism of L-asparaginase(L-ASP), which is efficient even for chemotherapy-resistant NK-cell lymphoma. First, L-ASP decreased expression levels of various translation initiation factors including eIF4E, which in turn suppressed the translation of MYC, BCL-2 and eIF4E itself with tumor promoting and apoptosis inhibiting activities. Second, L-ASP depleted glutamine, induced TCA cycle depletion and insufficiency, and finally caused apoptosis. The result showed glutamine addiction of various lymphoid malignancies including acute lymphoblastic leukemia and the central role of TCA cycle in the suppression of apoptosis.
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