Two alternative models describing 2 mechanisms of IR-induced apoptotic resistance in pediatric B-precursor ALL. (A) In most apoptosis-resistantALL tumors, the p53 pathway is functional, but increased prosurvival signals caused by hyperactive PARP1 or increased NF-κB activity outweigh the apoptotic signal transduced by p53. (B) In some tumors the apoptotic pathway is impaired by the mutation of TP53 or by inactivation of a gene upstream of p53. Therefore, tumor cells survive as a consequence of default prosurvival (eg, NF-κB–dependent) signals.