Targeting TBL1X is cytotoxic to MCL cells.TBL1X-specific shRNA KD in MCL cell lines (n = 2) using 2 constructs (sh425 and sh525) compared with an empty vector (EV) control: (A) TBL1X transcript levels (quantitative reverse transcription polymerase chain reaction, 1 day after transduction), (B) TBL1X protein levels (immunoblot, 4 days after transduction), and (C) cell viability. (D) Tegavivint sensitivity (IC50 at 24 hours) of 9 MCL cell lines (n = 9). (E) Cytotoxicity in samples from patients with MCL (n = 6) treated with tegavivint (18 hour). Subcutaneous murine MCL cell line model receiving tegavivint (n = 7; 30 mg/kg, IV, twice weekly) or VC (n = 7); (F) tumor volume at day 13 after engraftment and (G) Kaplan-Meier plot with log-rank Mantel-Cox analysis. Median OS was 20 days (range, 16-32) for drug-treated animals vs 16 days (range, 16-17) for VC-treated animals (P = .0230, hazard ratio = 2.213). Cell viability was determined for all experiments by annexin-V/PI staining and flow cytometry. Ann, annexin-V; FC, flow cytometry; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PI, propidium iodide. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.
