Modulation of the p53 pathway by ETV6/RUNX1 in childhood ALL

The t(12;21) is the most frequent translocation in childhood acute lymphoblastic leukemia generating the ETV6/RUNX1 (E/R) fusion gene. This fusion gene confers survival advantage and leads to clonal expansion of a preleukemic clone. It is, however, unable to generate overt leukemia by itself. Based on previous data suggesting that E/R interferes with p53 function, we investigated this issue further. p53 is a central regulator of the DNA damage response pathway and its activation leads to cell cycle arrest and DNA repair, apoptosis or senescence. Here, we show that E/R suppresses p53– and its downstream target p2…