Extended Data Figure 2. Silvestrol and the synthetic analogue (±)-CR-31-B are effective against T-ALL.

a) Dual luciferase reporter assay, shown are relative levels of each firefly (cap-dependent) and renilla (IRES-dependent) luciferase upon treatment with Silvestrol or (±)-CR-31-B. Mean and standard deviation are shown, n = 3 biological replicates; b) IC50 values for Silvestrol and CR in a panel of human T-ALL primary patient samples and cell lines. Mean and standard deviation are shown, n = 4 biological replicates; c) Silvestrol’s effect on murine T-ALLs with the indicated genetic lesions; curves are mean of triplicates and differences between the genotypes did not reach significance; d) Kaplan-Meier analysis showing time to leukaemia development after systemic transplantation of MOHITO cells in Balb/c mice followed by treatment on 7 consecutive days (treatments are indicated by red arrows) with either Silvestrol (0.5 mg/kg, red line, n = 5) or vehicle (black line, n = 5); e) KOPT-K1 xenograft studies. Shown is the tumour volume during and after systemic treatment with CR or vehicle (intraperitoneal injection, 0.2 mg/kg on days indicated by red arrows). Mean and standard deviation are shown, n = 6 biological replicates; f) Tumour volume upon intraperitoneal treatment with vehicle or Silvestrol (0.5 mg/kg on days indicated by red arrows). Mean and standard deviation are shown, n = 3 biological replicates.