The mechanism of nuclear pore-related leukemia

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790986
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: SHIMA Yutaka 独立行政法人国立がん研究センター, 研究所, 研究員 (90572298)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 白血病 / 核膜孔

Research Abstract

NUP98 is a component of the nuclear pore complex (NPC). The NUP98 gene is rearranged with several partner genes in acute myeloid leukemia and myelodysplastic syndromes and NUP98-related leukemia is known to have a poor prognosis. Although the NUP98 gene has the several fusion partners, the role of the NUP98 moiety of NUP98 fusion proteins is not well investigated. To investigate NUP98-fusion-interacting proteins,, we purified the protein complexes formed with NUP98-HOXA9. Mass spectrometry analysis identified that one metabolic regulator protein interacts with NUP98-HOXA9. The colony formation of the NUP98-HOXA9-immortalized mouse myeloid stem/progenitor cells was inhibited by shRNA and inhibitor for this metabolic protein. The inhibition was specific for NUP98 fusion-transformed cells. These results suggest that the metabolic protein can be a therapeutic target for NUP98 fusion-mediated leukemia.