Human T-ALL cell lines with high ZEB2 levels are sensitive to KDM1A inhibition. (A) Relative mRNA expression in a panel of human T-ALL cell lines analyzed by quantitative PCR. (B) Cell viability of human T-ALL cell lines with variable expression of ZEB2 mRNA after 12 days administration of the KDM1A inhibitor GSK2879552. The average and standard deviation of 2 independent experiments is plotted. (C) Cell viability of KARPAS-45 with doxycycline (dox)–inducible overexpression of ZEB2 vs parental line after 12 days of GSK2879552 administration. Western blot demonstrating level of dox-inducible ZEB2 overexpression (left); % of cell viability (right). (D) Differential gene expression after KDM1A inhibition (48 hours, 100 nM GSK2879552) in LOUCY (adjusted P value <.05, triplicates). (E) Preranked GSEA using probe set of genes upregulated upon KDM1A inhibition by tranylcypromine (TCP) in human AML cell lines.32 (F) ZEB2 and ITGAM mRNA expression levels upon siRNA-mediated ZEB2 knockdown in LOUCY cells (100 nM GSK2879552, 72 hours). (G) Analysis of CD11B protein expression by flow cytometry after KDM1A inhibition (100 nM GSK2879552, 72 hours) correlated with increased H3K4me2 levels at ITGAM promoter analyzed by ChIP.
