2016 Fiscal Year Final Research Report
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 |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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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 |
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| 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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| Free Research Field |
臨床検査医学
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