Fbxl10 overexpression leads to mitochondrial metabolic activation characterized by increased oxidative phosphorylation. (A) GSEA enrichment plot of KEGG OXPHOS gene set in nonleukemic (preleukemic) BM HSCs (HSCs from Tg mice vs HSCs from controls). Genes involved in OXPHOS were significantly enriched in Tg HSCs. Pooled RNAs from IL-7Rα− LSK HSCs in Tg and control individuals were used for the analysis. (B) GSEA enrichment plot of KEGG OXPHOS gene set in leukemic spleens (Tg leukemic spleens vs control spleens). Genes involved in OXPHOS were significantly enriched in Tg leukemic spleens. (C) Heat map of OXPHOS genes. Genes involved in OXPHOS are profoundly highly expressed in both pooled Tg HSCs and individual Tg leukemic spleens compared with the corresponding WT control HSCs and spleens. (D) Relative ATP levels in IL-7Rα− LSK HSCs of control and Tg mice at 20 weeks of age (n = 6 per group). Horizontal line, mean of ATP levels. Tg cells produced significantly more ATP than control cells (*P = .032). FDR, false discovery rate; NES, normalized enrichment score.