Investigating the role and therapeutic targets of cellular senescence in the development and transformation of myelodysplastic syndrome
| Project/Area Number |
17H06632
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Uni Masahiro 東京大学, 医学部附属病院, 特任臨床医 (20802359)
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 骨髄異形成症候群 |
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| Outline of Final Research Achievements |
With our Asxl1 heterozygous mutant knock-in mice, which recapitulates human myelodysplastic syndrome (MDS) well, we confirmed high expression of genes associated with cellular senescence, and also validated these in protein level. We further indicated the contribution of cellular senescence-related inflammatory cytokine secretion in the development of secondary leukemia from MDS. Finally, we intercrossed MDS model mice above with p16 knock-out mice, and showed restoration of phenotypes of human MDS in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
骨髄異型性症候群(MDS)は高齢者の高頻度に認められる予後不良の造血器腫瘍であるのみならず、急性骨髄性白血病への高頻度の進展も知られているが、MDSに対する現行の治療には根治的治療は含まれず、根本的な解決を得たとは言い難い。MDSの病態を捉え、それに適した治療法を開発することは喫緊の課題と言って良く、本研究はその治療標的の一端として細胞老化に可能性があることを見出した。これを標的とした治療がMDSに如何なる影響を及ぼすかについては、引き続き研究が必要とされる。
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Report
(3 results)
Research Products
(7 results)
