A MUTANT P53 ANTAGONIZES THE DEREGULATED C-MYC-MEDIATED ENHANCEMENT OF APOPTOSIS AND DECREASE IN LEUKEMOGENICITY

Myeloid leukemic M1 cells that do not express p53 and transfected M1 c lones that constitutively express the [Val(135)]p53 mutant or deregula ted c-myc or coexpressing both genes grew autonomously in culture with a similar growth rate and cloning efficiency. Expression of deregulat ed c-myc in M1 leukemic cells enhanced susceptibility to induction of apoptotic cell death and resulted in a reduced leukemogenicity when in jected into isologous mice. Expression of the [Val(135)]p53 mutant did not change cell susceptibility to induction of apoptosis or leukemoge nicity, but expression of this mutant p53 suppressed the effects of de regulated c-myc on these properties. The results indicate that the [Va l(135)]p53 mutant can show a gain of function for susceptibility to ap optosis and leukemogenicity in leukemic cells with deregulated c-myc a nd, thus, enhance tumor development.