Fig. 3

Genome-wide analysis of gene expression in CCRF-CEM cells. a MA plot of transcriptome profiling in FK866-treated vs. untreated CEM PA cells. For each gene, the average log₁₀ signal against the log₂ fold change is plotted. Genes significantly up (orange)- or down (violet)-regulated upon FK866 treatment are highlighted. b Top enriched gene ontology (GO) terms and KEGG pathways among up- and downregulated genes upon FK866 treatment in CEM PA and CEM RES cells. The heatmap, colored according to enrichment p values, displays categories associated with lysine acetylation, modulation of key epigenetic regulators, and transcription factors involved in energetic stress response. The number of genes corresponding to each term is reported in each tile. c MA plot of transcriptome profiling in FK866-treated vs. untreated CEM RES cells. For each gene, the average log₁₀ signal against the log₂ fold change is plotted. d CEM PA cells were treated with 5 and 100 nM FK866 for 48 h. Western blot showing expression of AMPK, mTOR, 4EBP1, and EIF2A in CEM PA cells. e No translation inhibition and drug-induced energetic stress occurs upon FK866 treatment in the resistance. Western blot analysis of CEM RES cells treated 100 nM FK866 for 48 h. Quantitative data are expressed as relative expression to MOCK (normalized by ACTIN). f CEM RES cells treated with 5 nM FK866 for 48 h. Expression of CHOP was determined. Quantitative data were derived from three independent experiments and expressed as the mean ± S.D. (***p < 0.001). g Barplot displaying genes belonging to the enriched metabolic pathways OXPHOS and glycolysis (KEGG annotation) and with significantly altered expression between CEM PA and CEM RES cells