Fig. 1
From: Harnessing the MYB-dependent TAL1 5’super-enhancer for targeted therapy in T-ALL
Mebendazole demonstrates anti-leukemic activity in 5’SE T-ALLs with poor clinical outcome due to MYB-mediated TAL1 inhibition. A 5’microinsertion sequences aligned to the normal physiological sequence (Hg38). The red arrow denotes the mutation insertion site. All TAL1 super-enhancer mutations introduce de novo MYB binding sites (underlined). B The relative TAL1 expression normalized to ABL + GAPDH expression in the thymus and T-ALL patients. Kruskal–Wallis; 5’SE vs. SIL-TAL1 p-adj = 0.5, 5’SE vs. TAL1-TCRD p-adj = 0.99, SIL-TAL1 vs. TAL1-TCRD p-adj = 0.97. C TAL1 protein expression in 5’SE compared with SIL-TAL1 T-ALL. Left Panel T-ALL cell lines, Right Panel PDX. Histone was used as a loading control. D Cumulative Incidence of relapse (CIR) of 5’SE, SIL-TAL1 and Other T-ALL. E Kaplan Meier depicting overall (OS) survival of 5’SE, SIL-TAL1 and other T-ALL. F Viability curves of 5’SE, SIL-TAL1, and Other T-ALL (Cell lines + PDX) at increasing Mebendazole concentrations. Viability was normalized to DMSO controls. The Mean and SEM are shown of duplicate samples. (Two-way ANOVA; 5’SE vs. SIL-TAL1 and Other T-ALL p < 0.0001). G MYB and TAL1 protein expression after 48 h Mebendazole exposure in the Jurkat cell line, a representative 5’SE, SIL-TAL1 and TAL1 negative (TAL1-) PDX with corresponding TAL1 mRNA expression for TAL1 + T-ALL (Right Panel). TAL1 expression was normalized to GAPDH