| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
|
|---|
| Outline of Final Research Achievements |
In the present study, we clarified molecular mechanisms of leukemia development by MEF2D-fusion gene and ZNF384-fusion gene, new recurrent gene abnormalities of acute lymphoblastic leukemia. MEF2D fusion gene evaded from the inhibition by miRNA, which caused higher expression of MEF2D fusion protein than wild-type MEF2D. Highly expressed MEF2D fusion protein inhibited the transcriptional activity of PAX5. We also revealed that ZNF384 fusion protein had stronger binding affinity to co-activator such as EP300 than wild-type, which lead to its stronger transcriptional activity. Furthermore, we performed drug screening to discover compounds that cause proteolysis of MEF2D-fusion protein. We found that staurosporine, a multi-kinase inhibitor, was a such drug and caused apoptosis of MEF2D-fusion gene positive ALL cell lines.
|
