Figure 2.

Opposing effects of individual PIDDosome components on c-Myc-induced lymphomagenesis. (a) Cohorts of Eμ-Myc (n=42), Eμ-Myc/Pidd^−/− (n=41) and Eμ-Myc/Casp2^−/− (n=25) mice were monitored for the development of B-cell lymphomas over time. Eμ-Myc mice lacking Caspase-2 showed a significantly earlier onset of lymphomagenesis (P=0.0044) compared with wt Eμ-Myc, while Pidd deficiency delayed lymphomagenesis in Eμ-mice (P=0.0005). (b) Distribution of pro/pre-B (white), mixed IgM^+/− (light gray), IgM⁺ (dark gray) and B220⁺CD4⁺ (black) lymphomas analyzed from mice of the indicated genotypes. The distribution of lymphomas in Eμ-Myc/Casp2^−/− was significantly different (P=0.004) compared with wt Eμ-Myc due to the higher amount of mixed and IgM⁺ tumors. Kaplan–Meier analysis was depicted as (c) pre-B and (d) IgM⁺ B lymphomas of indicated genotypes. In Eμ-Myc/Casp2^−/− mice, IgM⁺ tumors developed significantly earlier than in Eμ-Myc animals (P=0.0028). (e) Kaplan–Meier analysis of Bid^−/− (n=13), Eμ-Myc (median survival 97 d, n=18), Eμ-Myc/Bid^+/− (median survival 137 d, n=35) and Eμ-Myc/Bid^−/− (median survival 134 d, n=25) is shown. (f) Cohorts of Trail^−/− (n=22), Eμ-Myc (median survival 113 d, n=21), Eμ-Myc/Trail^+/− (median survival 125 d, n=50) and Eμ-Myc/Trail^−/− (median survival 164 d, n=20) mice were monitored for the development of B-cell lymphomas over time