Schematic illustration of Fbxl10-mediated leukemogenic processes. Fbxl10 induces leukemia involving metabolic proliferation advantage and impaired differentiation mediated by Nsg2. Fbxl10 confers HSCs on cell cycle progression through metabolic activation whereas Fbxl10 upregulates the expression of the Nsg2, impairing the differentiation of HSCs. Thus, Fbxl10 profoundly enhances leukemogenic potential/tumor susceptibility and leads to acute leukemia in mice after a long latency. Additional gene alterations and/or microenvironmental effects possibly intensify the proliferative potential and accelerate leukemic transformation mediated by Fbxl10 overexpression.