Indeed, we observed that primary CLL cells obtained from patients treated continuously with ibrutinib in vivo gain Akt phosphorylation on serine 473 (pAktS473) within several weeks on the therapy (in total 31 patients with 87 samples; fold-change 3.2 at week 4, P = 0.004; Figure 1, A and B). This evidence concerns the gene AKT1 and B-cell chronic lymphocytic leukemia.