Deguelin, a selective silencer of the NPM1 mutant, potentiates apoptosis and induces differentiation in AML cells carrying the NPM1 mutation.

摘要: Nucleophosmin (NPM1) is a multifunctional protein that functions as molecular chaperone, shuttling between the nucleolus and cytoplasm. In up to one third of patients with acute myeloid leukemia, mutation NPM1 results in aberrant cytoplasmic accumulation mutant thought be responsible for leukemogenesis. Deguelin, rotenoid isolated from several plant species, has been shown strong anti-tumor agent. Human leukemia cell lines were used vitro studies. Drug efficacy was evaluated by apoptosis differentiation assays, associated events assessed Western blot. Gene silencing performed using small interfering RNA (siRNA). Deguelin exhibited cytotoxic activity line OCI-AML3 selectively down-regulated protein, which accompanied up-regulation caspase-6 caspase-8 high concentrations. induced cells at nontoxic concentration decrease expression activated caspase-8, p53, p21, 30-kD form CCAAT/enhancer binding α (C/EBPα), whereas no effects found OCIM2 expressing NPM-wt. Moreover, treatment siRNA NPM decreased pro-caspase-8, C/EBPα, it inhibited proliferation cells. conclusion, deguelin potent inhibitor NPM1, provides basis its anti-leukemia activities