The clonal evolution of myeloma cells, the changes in the bone marrow microenvironment, the deregulation of microRNAs and the signaling interaction with the programmed death factor 1 (PD-1)/PDL1 contribute to the drug resistance noted in MM.31 The induction of the AKT/mTOR signaling by cytokines in the BM microenvironment mediates resistance to conventional and novel therapies. The gene discussed is AKT1; the disease is plasma cell myeloma.