Gata2 haploinsufficiency affects gene expression related to energy production and stress responses. (A) Histograms from gene set enrichment analyses using hallmark gene sets.²³  Six gene sets (oxidative phosphorylation, MYC targets v1, reactive oxygen species pathway, DNA repair, PI3K-AKT-mTOR signaling, and p53 pathway) were significantly enriched (nominal P value < .05 or false discovery rate [FDR] q value < 0.25) in genes upregulated in the 3q21q26::Gata2^+/− mice compared with the 3q21q26 mice. As genes related to oxidative phosphorylation, PI3K-AKT-mTOR signaling, and MYC targets are enriched in the 3q21q26::Gata2^+/− mice, we assume that 3q21q26::Gata2^+/− leukemic cells promote cell expansion supported by high-energy production based on productive oxidative phosphorylation. In addition, we surmise that the 3q21q26::Gata2^+/− leukemic cells acquire defenses to reactive oxygen species (ROS) after DNA damage as a consequence of oxidative phosphorylation and proliferation, because genes related on the ROS, DNA repair, and p53 pathways are enriched. In contrast, there was no gene set that was significantly enriched in genes downregulated in the 3q21q26::Gata2^+/− mice. The normalized enrichment scores (NES), the nominal P values and the FDR q values are indicated. (B) A scatter plot comparing transcript levels of the 3q21q26 mice (x-axis) and 3q21q26::Gata2^+/− mice (y-axis). Shown are 151 and 226 genes significantly upregulated or downregulated, respectively, in the 3q21q26::Gata2^+/− compared with the 3q21q26 leukemic mice. (C) Expression levels of the Gfi1b, Klf2, Pim1, and Evi5 mRNAs as fragments per kb of exon per million fragments read (FPKM). Bar graphs represent mean ± SD.