Small molecule-induced epigenomic reprogramming of APL blasts leading to antiviral-like response and c-MYC downregulation [ChIP-seq]

The epigenomic effects of maltonis, a novel maltol-derived molecule with promising antiproliferative activity against leukemic cells, have been characterized in the APL NB4 cell line. We demonstrate that maltonis treatments induce a profound remodulation of the histone code, reducing global H3K9me3 signal and modulating other histone post-translational modifications (HPTMs). Transcriptomic and epigenomic analyses revealed that maltonis exposure of NB4 cells induces changes in the expression of hundreds of genes (551 upregulated and 288 downregulated) in association with the modulation of the permissive HPTMs histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac) at their gene promoters. The upregulation of interferon alpha and gamma and the downregulation of c-MYC target genes have been identified as most significant pathways modulated by maltonis. Most importantly, c-MYC is strongly downregulated by maltonis and represents the common denominator of the downregulated gene sets, suggesting a central role of this gene in the biological response of NB4 cells to maltonis. NB4 cells were treated for 24 hours with maltonis 10 μM in vitro and analysed