LMP1 accelerates MYC-driven tumor onset but does not alter the number of p53 and/or p19^ARF abnormalities in λ-MYC tumors. (A) Kaplan-Meier curves indicate the percentage of tumor-free survival of indicated genotypes. Mice assigned for survival curve analysis were observed for tumor incidence. Days until the first sign of tumor is plotted as tumor-free survival. As found in our previous studies,³¹  LMP2A/λ-MYC mice are born with enlarged spleens, and lymphadenopathy can be readily detected by 5 to 6 weeks of age, whereas λ-MYC mice do not show splenomegaly or lymphadenopathy until they develop tumors. Mice between 4 and 6 weeks of age were classified as pretumor mice in our study. By 8 to 15 weeks of age, LMP1/λ-MYC and LMP2A/λ-MYC tumors are observed in cervical and axillary lymph nodes and then spread to other areas, including inguinal and abdominal lymph nodes. Tumor development in λ-MYC mice is generally observed after 20 to 30 weeks of age. In the mice of these ages, all tumors we analyzed showed a starry sky appearance typical for human BL. In contrast to LMP1/λ-MYC and LMP2A/λ-MYC tumors, primary organs in which λ-MYC tumors are first observed were not restricted to cervical areas but varied from cervical to abdominal areas. Tumor onset in λ-MYC mice in which tumors initiated in cervical areas was earlier (78.5 days, median survival) when compared with λ-MYC mice where tumors initiated in abdominal areas (156 days, median survival) (supplemental Figure 1C). Similar early- and late-tumor onsets were also reported in the studies of Eµ-Myc mice.⁵⁹  Even though tumor onsets in LMP1/λ-MYC and LMP2A/λ-MYC mice were significantly earlier than the onset of λ-MYC tumors in the cervical area. Log-rank (Mantel-Cox) test was used to compare survival curves. ****P < .0001. (B) The status of p53 and p19^ARF expression in lymph node tumors from the indicated genotypes as determined from immunoblots (supplemental Figure 2) are as indicated: p53⁺ and p19⁻, baseline p53 and p19^ARF levels; p53⁻, undetected baseline level of p53; p53⁺⁺, aberrant p53 accumulation at ∼53 kDa; p19⁺, abnormal accumulation of p19^ARF. Fisher’s exact test was used to compare the abnormalities of p53 and p19^ARF proteins. *P < .05, **P < .01, ***P < .001, and ****P < .0001. (C) Kaplan-Meier curves of tumor-free survival percentages with or without p53 and/or p19^ARF abnormalities indicated by “+” or “−”. P values were calculated by log-rank (Mantel-Cox) test.