The ARF/p53 and Atm/53 axes cooperate as proapoptotic growth restraints in Myc-driven tumorigenesis. (A) Genomic p53 status by allele-specific PCR in primary Eμ-myc lymphomas that formed in an Atm^+/+; p53^+/− or an Atm^−/−; p53^+/− background (normal tissue [N] compared with the matched tumor tissue [T] for every given animal); MEFs of the indicated p53 genotypes as controls. (B) Frequency of homozygous INK4a/ARF deletions that cancel ARF expression in control (ctrl) and Atm^−/− lymphomas detected by multiplex PCR of exon 1β and 2 (control, 8 of 19 cases; Atm^−/−, 5 of 14 cases tested). (C) Lymphoma incidence in lethally irradiated recipient mice of retrovirally bcl2-infected Eμ-myc transgenic Atm^+/+ and (control [ctrl]; n = 7; black) Atm^−/− (n = 6; red) hematopoietic stem cells. Note the very early onset due to the Bcl2 moiety (see Schmitt et al⁴⁵  for comparison with onset data upon mock infection). Immunoblot analysis testing for Bcl2 expression in lymphomas generated from transplanted bcl2- or mock-infected Eμ-myc hematopoietic stem cells (representative samples shown). (D) Immunoblot analysis of DDR components in ARF^−/−Eμ-myc lymphoma cell lysates exposed to adriamycin (ADR; 0.2 μg/mL for 5 hours) in vitro or left untreated.