These data indicate that PML-NBS integrity is necessary for a correct ATM–CHK2 axis activation.22 Furthermore, immunoblot analysis showed that H2AX, NBN, and CHK2 expression and phosphorylation levels were not affected in U937/PR9 cells treated or not with ZnSO4, then exposed to cycloheximide and finally irradiated, thus suggesting that de novo protein synthesis is not involved in the DDR signaling defects detected in APL cells (Figure 7c). This evidence concerns the gene PML and acute promyelocytic leukemia.