The non-genotoxic activator of the p53 pathway Nutlin-3 shifts the balance between E2F7 and E2F1 transcription factors in leukemic cells

Summary: The effect of Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, was investigated on the steady-state mRNA levels of the transcription factors E2F1 and E2F7 in a cohort of primary B-chronic lymphocytic leukemia (B-CLL) patient samples (n = 15) and normal peripheral blood mononuclear cells (PBMC). A 24-h treatment with Nutlin-3 significantly down-regulated E2F1 and promoted the concomitant up-regulation of E2F7 in both leukemic and normal cells. Our data suggest that the ability of Nutlin-3 to up-regulate E2F7 likely represents an important molecular determinant in the anti-proliferative activity of Nutlin-3.