Fig. 4
Unaltered or upregulated gene expression of KMT2A-fusion targets after acquired resistance to DOT1L inhibition. A. HOXA7, HOXA9, HOXA10, MEIS1, CKD6, and CCNA1 mRNA expression SEM and SEMPINO_RES cells cultured for 7 days in the absence (-) or presence (+) of 50 µM pinometostat, as determined by RNA-seq. Values indiacte normalized counts with standard deviation (SD) derived from four biological replicates for each cell line and condition. Differences in expression were statistically evaluated using unpaired t-tests; * p < 0.05, * p < 0.05, ** p < 0.005, *** p < 0.0005, **** p < 0.0001. Differences in chomatin accessibility at the HOXA, MEIS1, CKD6, and CCNA1 gene loci between SEMPINO_RES and SEM cells as determined by ATAC-sequencing by two biological replicates (on top). Vertical blue lines indicate significant decreases of chromatin accessibility in SEMPINO_RES cells, whereas grey lines indicate equal chromatin accessibility in both SEMPINO_RES and SEM. Red lines indicate significant increases in chromatin accessibility in SEMPINO_RES. Below the ATAC-sequencing data, ChIPseq tracks showning the presence of H3K79Me2, H3K27Ac, H3K4Me3, KMT2A, and AFF1 at the corresponding gene loci in SEM and SEMPINO_RES cells cultured for 7 days in the abscence (-) or presence (+) of 50 µM pinometostat