Fig. 2: Reduced inflammatory gene expression in CEBPA-mutant AML.
From: Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation
a GSEA of inflammatory response genes in CEBPA-mutant AML vs all the other AML mutants. Enrichment of (b) inflammatory response genes and (c) interferon alpha response genes in NRAS-, CEBPANT-, CEBPACT-, CEBPAbi- and STAG2- mutated AML, statistically tested by GSEA (NES=Normalized Enrichment Score). d Fold-change (log2) in expression of AP1/IFN/NFκB regulators in CEBPA-mutant AML. e Volcano plot of deregulated genes in KO-52p42 vs KO-52EV. Red: significantly upregulated genes (adj. p value < 0.05, log2FC > 1), blue: significantly downregulated genes (adj. p value < 0.05, log2FC < -1; n = 3 biological replicates). f Top 10 gene ontology terms of upregulated genes in KO-52p42 cells. g Normalized counts (rlog) of differentially expressed inflammatory genes in KO-52EV and KO-52p42, n = 3 biological replicates, two-sided unpaired t test. h GSEA of an AML inflammation signature56 in CEBPAbi/NT-mutated AML vs all the other AML mutants (top) and KO-52p42 vs KO-52EV (bottom). NES normalized enrichment score. i Expression (z-score) of AP-1 family members grouped by subfamily in three replicates (each individual column is a replicate) of KO-52EV and KO-52p42. Left column (DE) indicates the differential expression status. Red: upregulated genes, blue: downregulated genes, gray: non-significantly changed genes (p-adj <0.05 log2FC <|0 | ). j Overlap of downregulated genes in p30-expressing cells in the different models. k Top 10 gene ontology terms enriched in p30-dependent genes common to: CEBPA-mutant AML, p30 hematopoietic progenitors, KO-52p42 and p30-HPC-7. n = 3 biological replicates. d, g Boxplots: center lines represent the median, lower and upper hinges correspond to the first and third quartiles (25th and 75th percentiles). Upper whisker extends from the hinge to the largest value no further than 1.5 * IQR from the hinge (IQR, inter-quartile range). Lower whisker extends from the hinge to the smallest value at most 1.5 * IQR of the hinge. d, e, i Statistical test used: Wald test, using Benjamini-Hochberg test for adjustment for multiple comparisons. f, k Fisher’s exact test.
