Targeting Group3 Medulloblastoma by the anti-PRUNE-1 and anti-LSD1- KDM1A molecules augments their potential therapeutic value.

The combination of AA7.1 and SP2577 affects neuronal commitment,leukocyte differentiation and mitochondrial metabolism. To better dissect the mechanisms of action of these two drugs and to investigate the genes and pathways affected we treated primary Group3 MB for 24 hours with 100µM AA7.1 (pruneinhibotor) , 22.5µM SP2577 ( LSD1 inhibitor) and the combination and we performed RNA-Seq. Vehicle treated cells were used as control. Gene expression analysis showed up-regulation of genes implicated in neuronal differentiation, mitochondrial metabolism in cells treated with Prune-1 and LSD1 inhibitors, with stronger evidence in cells treated with the combination of two drugs.