| Project/Area Number |
26860742
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | National Cancer Center Japan |
|---|
Principal Investigator |
Shima Yutaka 国立研究開発法人国立がん研究センター, その他部局等, 研究員 (90572298)
|
|---|
| Project Period (FY) |
2014-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | leukemia / NUP98 |
|---|
| Outline of Final Research Achievements |
We have identified that NUP98-HOXA9 interacts with FASN and orlistat, which is the inhibitor of FASN, selectively inhibits the colony formation of NUP98 fusion protein-expressing cells. To measure the amount of each metabolite in NUP98 fusion protein- and other fusion protein-expressing cells and normal hematopoietic cells, we performed CE-MS analysis. However, the status of metabolites in NUP98 fusion protein-expressing cells was not significantly different from the other cells. Next, we focused on fatty acids. In vitro analysis showed that NUP98-HOXA9 reduced the FASN activity. Furthermore, LC-TOFMS analysis showed that the amount of fatty acids in NUP98-HOXA9-expressing cells was less than in normal hematopoietic cells. The inhibition of FASN resulted in S-phase arrest in NUP98-HOXA9-expressing cells. These results suggest that FASN activity is low but is essential for NUP98 fusion-mediated leukemia cells, and that FASN can be a therapeutic target for the leukemia.
|
