Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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Outline of Final Research Achievements |
In the EVI1-GFP knock-in retrovirally induced MLL-ENL murine AML model, HSC-like and GMP-like AML cells were sorted by GFP expression and compared for gene expression pattern. The HSC-like AML cells induce refractory AML despite low leukemia stem cell frequency. The HSC-like AML cells were characterized by enrichment of the NF-κB pathway, chemotherapy resistance-related gene cluster, and elevated chemokine expression, consistent with the phenotype of HSC-like AML cells. The EVI1-high AML model with HSC-like expression patterns also shared the same transcriptional profile as HSC-like AML cells: the immune-related pathways, including chemokines and IFN-γ pathway, which were regulated by cyclin D1. We also demonstrated that the genetic modification of Cyclin D1, chemokine and IFN-γ pathway can suppress AML development.
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