Our data may generate hypotheses for the development of genetic instability in CML, in which γH2AX and 53BP1 foci accumulate with ongoing DNA damage by intrinsic sources (e.g., reactive oxygen species, replication-stress-induced DNA damage), erroneous DSB repair (e.g., NHEJ and MMEJ), and alterations of the DDR (e.g., sensing and signaling of DNA damage) (Figure 4). This evidence concerns the gene TP53BP1 and chronic myelogenous leukemia, BCR-ABL1 positive.