RNA sequencing was performed on biological triplicates of HSB2 and RPMI8402 cells treated with 100nM GSK2879552 for 48h versus their corresponding DMSO treatment controls. GSK2879552 is a potent, selective and orally bioavailable inhibitor of the lysine-specific histone demethylase 1 (LSD1). Gene expression was severely affected by LSD1 inhibition.  Pathway analysis performed on the differentially expressed genes following 48hrs of LSD1i treatment clearly showed an increased apoptotic gene signature (CASP3, CASP8) and enhanced expression of genes associated with TRAIL signaling. Furthermore, pre-ranked Gene Set Enrichment Analysis (GSEA) revealed that genes upregulated after LSD1 inhibition in  HSB2 showed significant enrichment for transcripts that are down in hematopoietic stem cells and early T lymphocytes. In contrast, important components of the Notch, WNT and SMAD signalling complex were significantly down regulated upon short-term LSD1i treatment in HSB2  cells. In line with this notion, pre-ranked GSEA also revealed that LSD1i resulted in decreased expression of genes that significantly overlap with an oncogenic MYC signature. SOURCE: Sofie Peirs (sofie.peirs@ugent.be) -  Ghent University

Pluto Bioinformatics

GSE90657: Effect of 48h treatment with 100nM GSK2879552 on T-ALL cell lines HSB2 and RPMI8402