Atorvastatin prevented the onset of MYC-induced lymphomagenesis. (A) Atorvastatin treatment of mice expressing MYC. Kaplan-Meier survival curves of transgenic mice conditionally overexpressing the MYC transgene in murine T-cell lymphocytes using the Tet-system (MYC ON; n = 16) or treated with doxycycline to suppress MYC expression (MYC OFF; n = 5). Mice overexpressing MYC (MYC ON) were treated with atorvastatin 3 times weekly (MYC ON + AT1, 1 mg/kg; n = 16), (MYC ON + AT10, 10 mg/kg; n = 11), or (MYC ON + AT100, 100 mg/kg; n = 16) as indicated. Mice overexpressing MYC were treated with atorvastatin (100 mg/kg) and mevalonate (20 mg/kg) (MYC ON + AT100 + Mev; n = 13). Significant difference in survival was determined by Chi square test (P < .001; MYC ON + AT100 100 mg/kg). (B) Atorvastatin treatment of mice expressing MYC and constitutively activated K-Ras (G12D). Survival curve of mice overexpressing MYC alone (MYC ON; n = 14) or together with activated murine K-Ras (G12D) (MYC/Ras ON; n = 8) or treated 3 times weekly with 100 mg/kg atorvastatin (MYC/Ras ON + AT100, 100 mg/kg; n = 11). (C) Atorvastatin treatment prevents tumor onset in mice given transplants of bone marrow from MYC transgenic mice. Lethally irradiated mice were given transplants of bone marrow cells (5 × 10⁶) pooled from 3 mice that overexpress MYC. Mice were treated with doxycycline to inactivate MYC (MYC OFF; n = 5), not treated with doxycycline (MYC ON; n = 5), or not treated with doxycycline but treated with atorvastatin (AT100, 100 mg/kg; n = 5) 3 times weekly. Significant difference in survival of atorvastatin-treated mice compared with nontreated mice was determined by Chi square test (P < .001). (D) In vitro purging of bone marrow from MYC transgenic mice with atorvastatin prevents tumor development. Bone marrow of MYC-overexpressing mice with tumor burden was treated in vitro with atorvastatin (10 μM) for 24 hours (n = 5), 30 hours (n = 5), or for 48 hours (n = 5). Treated or nontreated bone marrow cells (5 × 10⁶) were injected into lethally irradiated mice. Significant difference in survival was determined by Chi square test (24 hours, P > .04; 30 hours, P < .002; 48 hours, P < .001). (E) Transient treatment with atorvastatin delays tumor onset. Transgenic mice conditionally overexpressing MYC were either treated with doxycycline for 6 weeks (MYC OFF, 6 weeks; n = 9) or not treated with doxycycline (AT 100 mg/kg, 6 weeks; n = 14) but treated with atorvastatin at 100 mg/kg 3 times weekly for 6 weeks (n = 13) when weaned. The difference in survival of atorvastatin-treated mice was compared with that of nontreated mice using the Chi square test (P < .001).