AKT/mTOR signaling activation has been characterized as an important resistance mechanism in IB-R mantle cell lymphoma [50], Waldenstrom macroglobulinemia [51], CLL, and DLBCL [18], as well as venetoclax-resistant [52], or fludarabine-resistant [53] B-cell lymphoid malignancies, where inhibition represented a powerful approach to overcome drug resistance and induce apoptosis. The gene discussed is MTOR; the disease is Waldenstrom macroglobulinemia.