Figure 4.
PI3Kγ maintains the nucleotide metabolism of LSCs. (A) GO (biological process) analyses were performed with transcriptome data of WT and Pik3cg-KO BM L-GMP cells at 4 weeks after primary transplantation (n = 3 mice per group). (B-C) Gene set enrichment analyses evaluating changes in purine metabolism (B) and pyrimidine metabolism (C) in WT and Pik3cg-KO BM L-GMP cells at 4 weeks after primary transplantation. (D) Pyrimidine and purine metabolite changes in WT and Pik3cg-KO BM L-GMP cells measured via metabolomics at 4 weeks after primary transplantation (n = 6). (E) Nucleoside partial rescue of growth inhibition of Pik3cg-KO BM AML cells in liquid culture at 4 weeks after primary transplantation (n = 3). (F-G) Colony numbers (F) and their derived cell counts (G) were determined 6 days after WT and Pik3cg-KO BM L-GMP cells were seeded in the methylcellulose medium containing nucleosides at 4 weeks after primary transplantation (n = 3). (H) The metabolites in the nucleotide synthesis were measured in WT, Pgd-overexpressing WT, Pik3cg-KO, and Pgd-overexpressing KO L-GMP cells and normalized against WT+vector cells 4 weeks post-transplantation (n = 5). Data are represented as mean ± SEM. Student 2-tailed unpaired t test for panel D and 1-way ANOVA with Tukey’s multiple comparison test for panels E-G were used for the comparison of statistical significance. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.

PI3Kγ maintains the nucleotide metabolism of LSCs. (A) GO (biological process) analyses were performed with transcriptome data of WT and Pik3cg-KO BM L-GMP cells at 4 weeks after primary transplantation (n = 3 mice per group). (B-C) Gene set enrichment analyses evaluating changes in purine metabolism (B) and pyrimidine metabolism (C) in WT and Pik3cg-KO BM L-GMP cells at 4 weeks after primary transplantation. (D) Pyrimidine and purine metabolite changes in WT and Pik3cg-KO BM L-GMP cells measured via metabolomics at 4 weeks after primary transplantation (n = 6). (E) Nucleoside partial rescue of growth inhibition of Pik3cg-KO BM AML cells in liquid culture at 4 weeks after primary transplantation (n = 3). (F-G) Colony numbers (F) and their derived cell counts (G) were determined 6 days after WT and Pik3cg-KO BM L-GMP cells were seeded in the methylcellulose medium containing nucleosides at 4 weeks after primary transplantation (n = 3). (H) The metabolites in the nucleotide synthesis were measured in WT, Pgd-overexpressing WT, Pik3cg-KO, and Pgd-overexpressing KO L-GMP cells and normalized against WT+vector cells 4 weeks post-transplantation (n = 5). Data are represented as mean ± SEM. Student 2-tailed unpaired t test for panel D and 1-way ANOVA with Tukey’s multiple comparison test for panels E-G were used for the comparison of statistical significance. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.

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