As the overactivation of NHEJ activity in R-CLL is correlated with enhanced DNA end-binding of Ku70/Ku80 heterodimer without an increase in its expression [11], we next hypothesized that the post-translational modifications (PTMs) of Ku may be a critical step in the development of aggressive forms of CLL. This evidence concerns the gene XRCC6 and B-cell chronic lymphocytic leukemia.