Figure 3

In vivo and in vitro phenotype of isogenic EBV-positive and EBV-loss BL clones. (a) Tumorigenicity of BL clones in NSG mice. Kaplan–Meier survival plots comparing survival in days post inoculation (P.I.) with isogenic EBV-positive (blue) or EBV-loss clones (red) derived from the parental EBV-positive BL cells lines as indicated. Kem-BL clones, EBV-positive n=12, EBV-loss n=24, median survival (MS) 54versus 102 days. Mutu-BL clones, EBV-positive n=19, EBV-loss n=29, MS 63versus 113 days. Awia-BL clones, EBV-positive n=12, EBV-loss n=12, MS 50versus 68 days. (b) Apoptotic cell death induced in response to BCR crosslinking with anti-IgM antibodies in isogenic EBV-positive (P1–P3) versus EBV-loss (n1–n3) clones of Kem-BL, Mutu-BL and Awia-BL, 72 h post-treatment compared with vehicle-only controls. (c) Ionomycin-induced cell death in isogenic EBV-positive (P1–P3) versus EBV-loss (n1–n3) clones of Kem-BL, Mutu-BL and Awia-BL (48 h), compared with vehicle-treated controls. Data are the mean and standard deviation (S.D.) of pooled data from three independent experiments, each carried out in triplicate. Unpaired, two-tailed Student’s T-tests were carried out to assess the significance of any difference in response between EBV-positive and EBV-loss clones from each background and P-values are indicated. Additionally, a two-way analysis of variance (ANOVA) to compare all clones from all BL tumours showed that overall EBV has a highly significant effect on cell survival (P<0.0001) in response to both ionomycin and IgM crosslinking