Disruption of PML-NBs by PML-RARα is a hallmark of APL, a model disease to understand leukemogenic pathways directed by an oncoprotein.24, 25, 26, 27, 28, 29, 30, 31, 32 Here, we report that PML-NBs play a key role in regulating early and late steps of IR-induced DSBs sensing, signaling, and repair in myeloid cells in vitro and in vivo. Here, PML is linked to acute promyelocytic leukemia.