Fig. 6: Prognostic value of KDM5C expression in human AML.

A Doubling time (hours) of control and KDM5C-KD HL-60 cells. B Relative mRNA expression of KDM5C in HL-60 control and KDM5C-KD groups assayed by RT-qPCR and normalized to POLR2A expression. C Doubling time (hours) of control and KDM5C-KD NB-4 cells. D Relative mRNA expression of KDM5C in NB-4 control and KDM5C-KD groups assayed by RT-qPCR and normalized to POLR2A expression. E Correlation between KDM5C expression and overall survival status in female patients (TCGA dataset). P-value was calculated by unpaired two-tailed T-test with Welch’s correction. F Overall survival of female AML patients (TCGA dataset) grouped according to High (above median) and Low (below median) expression of KDM5C as indicated. Patients with survival times less than six months were excluded from the analysis. G Correlation between KDM5C expression and disease-free survival status in female patients (TCGA dataset). P-value was calculated by unpaired two-tailed T-test with Welch’s correction. H Disease-free survival of female AML patients (TCGA dataset) grouped according to High (above median) and Low (below median) expression of KDM5C. Patients were excluded as in (F). I Most frequent mutations found in top/bottom 25% of KDM5C High and Low female patients (TCGA dataset). P-values determined by Fisher’s exact test. J Model of KDM5C function in AML. Decreased Kdm5c expression leads to a general enrichment of H3K4me3 at KDM5C-targeted genes, providing leeway for increased expression from bivalently marked gene promoters (low-activity) without affecting highly active genes. These KDM5C-targeted bivalent genes are expressed in immature differentiation stages, thus their upregulation in Kdm5c-KD Lp30 cells results in a tumor-advantageous de-differentiation.