Modulation of SLC7A11 alters ALL cell line sensitivity to LASP. (A-B) Rescue of LASP-mediated cell death by sulfasalazine in Nalm6 (A) and SUPB15 (B) cells. Each cell line was treated with sulfasalazine (SAS; 500 µM or 1 mM), LASP (0.001 IU/mL, 1 IU/mL, and 10 IU/mL), or both drugs for 12 hours before assessment of cell viability (t test; P ≤ .05; n = 4 independent experiments; mean ± SEM). (C) Relative SLC7A11 overexpression in 697 cells (n = 3 independent experiments). (D) Dose–response (left) after 24 hours of LASP treatment following transient overexpression of SLC7A11 in 697 cells and changes in area under the curve (AUC) (right, P < .05; n = 3 independent experiments; mean ± SEM). (E) Change in cell viability between control and SLC7A11 overexpressing 697 cells as fold change relative to control cells is shown after 1 IU/mL (left) and 10 IU/mL (right) of LASP treatment for 24 hours (P < .01; n = 12 independent experiments; mean ± SEM). (F) Depiction of the edited region of SLC7A11 gene sequence in exon 2 in Nalm6 cells. WT = SLC7A11 wildtype, INS = SLC7A11 insertion. (G) Dose–response (left) after 72 hours of LASP treatment and changes in AUC (right) in Nalm6 SLC7A11-disrupted cells (SLC7A11^wt/ins) compared with wildtype Nalm6 cells (SLC7A11^wt/wt; P < .05; n = 3 independent experiments; mean ± SEM). (H) Change in cell viability between SLC7A11^wt/wt and SLC7A11^wt/ins Nalm6 cells as fold change relative to wild-type cells is shown after 0.0001 IU/mL (left) and 0.0006 IU/mL (right) of LASP treatment for 72 hours (P < .01; n = 18 independent experiments; mean ± SEM).