CEBPB promotes myeloid differentiation and dysregulates IL-1/TNF and apoptosis pathway members. (A) The volcano plot shows the CEBPB correlated genes from the Beat AML cohort as determined by Spearman correlation coefficient tests. The plot illustrates a positive correlation between CEBPB expression and inflammatory genes, whereas a negative correlation is observed with apoptosis-related genes. (B) Flow cytometry histograms illustrate the upregulation of CD11b and CD14 expression in CEBPB overexpressing cells. (C) This graph shows the log fold changes in the RNA expression of apoptosis-related genes for the comparison between the M4/M5 and M0/M1 primary patient samples. Genes with statistically significant differences also in protein expression are highlighted in the bold black boxes. The apoptosis pathway depicted was derived from Reactome. (D) The graphs depict the RNA expression for CASP6 and TNF during hematopoiesis. (E) The volcano plot highlights the differentially expressed inflammation and apoptosis-related genes obtained from the RNA-seq data of OCIAML3 cells that overexpressed CEBPB in comparison with the empty vector control in duplicates. (F) The immunoblot analysis showed upregulation of CEBPB and MDM2 and downregulation of CASP3 and CASP6 in MOLM14 and OCIAML3 cells that overexpressed CEBPB, whereas increased CASP3 and CASP6 were observed in cells that expressed single guide RNA (sgRNA) that targeted CEBPB. (G) This graph depicts the correlation coefficients (r values) for the comparison of apoptosis-related gene RNA expression and the drug AUCs of idasanutlin and/or venetoclax. Genes with protein levels that showed a significant correlation with the AUC of both drugs are highlighted with black bold dashed lines. The apoptosis pathway depicted was derived from Reactome. (H) The competitive drug assay graphs depict the relative percentage changes in the population of MOLM14 and OCIAML3 cells that overexpressed CASP3 or CASP6 when treated with venetoclax or idasanutlin, normalized to their initial population. (I) Graphs showing the mean viabilities (of 3 technical replicates) of the MOLM14 and OCIAML3 cells, transduced with a virus that encoded an MCL1 overexpression vector or CRISPR/Cas9 sgRNA that targeted CASP, following treatment with venetoclax or idasanutlin as determined by MTS-based viability assays. Ida, idasanutlin; Ven, venetoclax; sgRNA, single-guide RNA.

CEBPB promotes myeloid differentiation and dysregulates IL-1/TNF and apoptosis pathway members. (A) The volcano plot shows the CEBPB correlated genes from the Beat AML cohort as determined by Spearman correlation coefficient tests. The plot illustrates a positive correlation between CEBPB expression and inflammatory genes, whereas a negative correlation is observed with apoptosis-related genes. (B) Flow cytometry histograms illustrate the upregulation of CD11b and CD14 expression in CEBPB overexpressing cells. (C) This graph shows the log fold changes in the RNA expression of apoptosis-related genes for the comparison between the M4/M5 and M0/M1 primary patient samples. Genes with statistically significant differences also in protein expression are highlighted in the bold black boxes. The apoptosis pathway depicted was derived from Reactome. (D) The graphs depict the RNA expression for CASP6 and TNF during hematopoiesis. (E) The volcano plot highlights the differentially expressed inflammation and apoptosis-related genes obtained from the RNA-seq data of OCIAML3 cells that overexpressed CEBPB in comparison with the empty vector control in duplicates. (F) The immunoblot analysis showed upregulation of CEBPB and MDM2 and downregulation of CASP3 and CASP6 in MOLM14 and OCIAML3 cells that overexpressed CEBPB, whereas increased CASP3 and CASP6 were observed in cells that expressed single guide RNA (sgRNA) that targeted CEBPB. (G) This graph depicts the correlation coefficients (r values) for the comparison of apoptosis-related gene RNA expression and the drug AUCs of idasanutlin and/or venetoclax. Genes with protein levels that showed a significant correlation with the AUC of both drugs are highlighted with black bold dashed lines. The apoptosis pathway depicted was derived from Reactome. (H) The competitive drug assay graphs depict the relative percentage changes in the population of MOLM14 and OCIAML3 cells that overexpressed CASP3 or CASP6 when treated with venetoclax or idasanutlin, normalized to their initial population. (I) Graphs showing the mean viabilities (of 3 technical replicates) of the MOLM14 and OCIAML3 cells, transduced with a virus that encoded an MCL1 overexpression vector or CRISPR/Cas9 sgRNA that targeted CASP, following treatment with venetoclax or idasanutlin as determined by MTS-based viability assays. Ida, idasanutlin; Ven, venetoclax; sgRNA, single-guide RNA.

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