| Budget Amount *help |
¥41,080,000 (Direct Cost: ¥31,600,000、Indirect Cost: ¥9,480,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2016: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2015: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2014: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
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| Outline of Final Research Achievements |
We performed functional study of Down syndrome associated acute megakaryocytic leukemia (DS-AMKL)-specific mutations to understand the mechanisms of multistep leukemogenesis in DS, and found the following results.
1）We found many novel recurrent mutations in DS-AMKL samples using whole exome sequencing, and performed functional study for these mutations. 2）We established the K562 subclones expressing GATA1s exclusively (GATA1s subclones) using CRISPR/Cas9 gene editing. GATA1s subclones expressed KIT at higher levels compared to the wild type K562. Engineered DNA-binding molecule-mediated ChIP (enChIP) sequencing and 3C-based proximity ligation assays revealed that in the GATA1s subclone, GATA1-binding region at -87 kb with respect to the transcription start site was more proximate to the KIT transcriptional start site compared to the wild type, suggesting that the N-terminal domain of GATA1 is essential for proper genomic conformation and gene expression regulation of KIT.
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