Development of a novel mechanism of T-ALL and its clinical application for the diagnosis and treatment.
Project/Area Number |
26460667
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Laboratory medicine
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Research Institution | Chiba University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
野村 文夫 千葉大学, 医学部附属病院, 特任教授 (80164739)
星野 忠次 千葉大学, 大学院薬学研究院, 准教授 (90257220)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | T細胞性急性リンパ性白血病 / 質量分析 / モデルマウス / c-myc / PKM2 / PUF60/FIR / 急性リンパ性白血病 / 癌糖代謝 / c-myc / スプライシング / 急性Tリンパ性白血病 / 転写因子 / T細胞性急性リンパ性白血病 / c-myc遺伝子 / 臓器浸潤 / ノックアウトマウス / 機能解析 |
Outline of Final Research Achievements |
The switch of pyruvate kinase (PK) M1 and PKM2 is pivotal for glucose metabolism in cancers. FUSE-binding protein (FBP)-interacting repressor (FIR) is a transcriptional repressor of the c-myc gene. This study investigated the thymic lymphoma tissues of mice and revealed that haplodeficiency of FIR significantly contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma using six-plex tandem mass tag (TMT) quantitative proteomic analysis in this mice model. TMT revealed 648 proteins that were up- or downregulated in mice thymic lymphoma tissues. Among them, PKM2 protein, but not PKM1, was upregulated in the thymic lymphoma as well as T-ALL. These results indicated that FIR haplodeficiency contributes the alternative splicing of PKM1 to PKM2 by partly inhibiting hnRNPA1 expression in the thymic lymphoma cells prior to T-ALL. Taken together, our findings suggest that FIR and its related spliceosomes are potential therapeutic targets for cancers, including T-ALL.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Anti-FIRs (PUF60) auto-antibodies are detected in the sera of early-stage colon cancer patients.2016
Author(s)
Kobayashi S, Hoshino T, Hiwasa T, Satoh M, Rahmutulla B, Tsuchida S, Komukai Y, Tanaka T, Matsubara H, Shimada H, Nomura F, Matsushita K
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Journal Title
Oncotarget
Volume: 7
Issue: 50
Pages: 82493-82503
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation.2016
Author(s)
Ishige T, Nishimura M, Satoh M, Fujimoto M, Fukuyo M, Semba T, Kado S, Tsuchida S, Sawai S, Matsushita K, Togawa A, Matsubara H, Kaneda A, Nomura F
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 21681-21681
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Haploinsufficiency of the c-myc transcriptional repressor FIR, as a dominant negative-alternative splicing model, promoted p53- dependent T-cell acute lymphoblastic leukemia progression by activating Notch1.2015
Author(s)
Matsushita K, Kitamura K, Rahmutulla B,, Tanaka N, Ishige T, Satoh M, Hoshino T, Miyagi S, Mori T, Itoga S, Shimada H, Tomonaga T, Kito M, Nakajima-Takagi Y, Kubo S, Nakaseko C, Hatano M, Miki T, Matsuo M, Fukuyo M, Kaneda A, Iwama A and Nomura F.
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Journal Title
Oncotarget.
Volume: 6
Pages: 5102-17
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Sendai virus-mediated c-myc suppressor far-upstream element binding protein interacting repressor gene transfer suppresses head and neck squamous cell carcinoma.2015
Author(s)
Tanaka N, Araki K, Mizokami D, Miyagawa Y, Yamashita T, Tomifuji M, Ueda Y, Inoue M, Hasegawa M, Matsushita K, Nomura F, Shimada H, Shiotani A.
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Journal Title
Gene Therapy
Volume: 22
Pages: 297-304
Related Report
Peer Reviewed / Open Access
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[Journal Article] Alternative splicing of FBP-interacting repressor coordinates c-Myc, P27Kip1/cyclinE and Ku86/XRCC5 expression as a molecular sensor for bleomycin-induced DNA damage pathway.2014
Author(s)
Rahmutulla B, Matsushita K, Satoh M, Seimiya M, Tsuchida S, Kubo S, Shimada H, Ohtsuka M, Miyazaki M, Nomura F.
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Journal Title
Oncotarget
Volume: 5
Pages: 2404-17
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Alternative splicing rather than haploinsufficiency of c-myc transcriptional repressor, FIR, promotes P53-dependent T-cell lymphoblastic leukemia progression.2014
Author(s)
Matsushita K, Kitamura K, Bahityar R, Hoshino T, Iwama A, Shimada H, Tomonaga T, Kubo S, and Nomura F.
Organizer
The 73rd annual meeting of the Japanese cancer association
Place of Presentation
Yokohama・パシフィコ横浜
Year and Date
2014-09-25 – 2014-09-27
Related Report
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