Fig. 7

Exportin 1 (XPO1) inhibitors selectively kill TET2-mutant MV4-11 cells. (A, B) TET2 wild-type (WT) MV4-11 leukaemia cells and two clones created using different CRISPR guides of CRISPR-cas9-induced, TET2-inactivated MV4-11 cells were cultured with different concentrations of selinexor (A) or eltanexor (B) for 72 h. Cell viability was measured with the Cell-Titre Glo assay and the inhibitory concentration at 50% (IC50) is indicated for each group. Data represent the mean ± SD of three independent experiments. (C) TET2 WT and -mutant MV4-11 clones were treated with dimethylsulfoxide (DMSO), or 20 nM selinexor or 20 nM eltanexor for 16 h (for cleaved PARP and cleaved-Caspase3) and analysed by western blot. This experiment was performed three times with qualitatively similar results. (D) TET2 WT and two independent clones of CRISPR-cas9-induced, TET2-mutant MV4-11 cells were plated on methylcellulose containing (DMSO, selinexor (20 nM) or eltanexor (20 nM). The total number of colony-forming units (CFUs) was determined after 7 days.