We also found that PD-L1 binding with PD-1-Fc beads in myeloma cells induced resistance to anti-myeloma agents, such as melphalan and bortezomib, accompanied by the activation of the PI3K/AKT signaling pathway, because PD-1−PD-L1 bingeing delivered a reverse signal from PD-L1 into myeloma cells with the upregulation of CCND3, BCL2 and MCL1 [79]. This evidence concerns the gene AKT1 and plasma cell myeloma.