Page 90 - Haematologica - Vol. 105 n. 6 - June 2020

N. Maslah et al.
hand, the combination of the two drugs (APR + AZA) had a similar effect as APR on its own in progenitor cells from patients with WT TP53, whereas the combination had a significantly more pronounced effect than APR on its
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own on progenitor cells from patients with mutant TP53. This strongly suggests a selective effect on mutant p53 cells, although we were unable to demonstrate the forma- tion of wild-type TP53 colonies under treatment, which
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Figure 6. Changes in gene expression induced by treatment with PRIMA-1Met (APR-246, APR) + azacitidine (AZA). (A) A Venn diagram representing the number of deregulated genes with APR on its own, AZA on its own, or the combination of APR + AZA. (B) Gene enrichment plots and associated heatmaps showing reactivation of the p53 pathway and induction of an apoptosis program in SKM1 cells treated with IC10 APR compared to untreated cells. (C) Gene enrichment plots and associated heatmaps showing reactivation of the p53 pathway and induction of an apoptosis program in SKM1 cells treated with the combination of APR IC10 + AZA IC50 (APR + AZA) compared to AZA on its own (AZA). (D) RT-qPCR expression of the main p53 targets (CDKN1A and BAX) and pro-apoptotic factors (CASP1 and FAS) in SKM1 cells treated with APR compared to untreated cells. (E) RT-qPCR expression of the main p53 targets (CDKN1A and BAX) and pro-apoptotic factors (CASP1 and FAS) in SKM1 cells treated with the combination of APR + AZA versus AZA on its own. ***P<0.001. NES: Normalized Enrichment Score; FDR: False Discovery Rate.
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