Therefore, while confirming that Ibrutinib (either alone or in combination with Nutlin-3) marked counteracts the MAPK and PI3K/AKT pathways in B-CLL, we have provided evidence that the synergistic anti-leukemic activity of the Ibrutinib/Nutlin-3 combination have a convergence point in regulating cell survival/death through the activation of the DDR signaling. This evidence concerns the gene AKT1 and B-cell chronic lymphocytic leukemia.