Mutant mice lacking alternatively spliced p53 isoforms unveil as a male-specific prognostic factor in Myc-driven B-cell lymphomas.

The gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the alternatively spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in males compared to males, but also compared to and females. Pre-tumoral splenic cells from males exhibited a higher expression of encoding an atypical chemokine receptor with tumor suppressive effects. We identified as a p53 target gene whose p53-mediated transactivation is inhibited by estrogens, and as a male-specific factor of good prognosis relevant for murine -induced and human Burkitt lymphomas. Furthermore, the knockout of increased the chemokine-guided migration of Burkitt lymphoma cells. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven lymphomagenesis.