Metabolic Disorder in NUP98 Fusion Gene-Induced Leukemia

2015 Fiscal Year Final Research Report

• 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
• 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.

Free Research Field

血液腫瘍学