Therapeutic drug–induced up-regulation of NKG2D and DNAM-1 ligands on patient-derived malignant PCs contributes to the degranulation of autologous NK cells. Mononuclear cells derived from the BM of the patients were prepared as described in “Cell lines and clinical samples,” treated with melphalan (20 μM) or bortezomib (5 nM) for 48 hours, then compared with untreated cells for their capability to enhance NK-cell degranulation. Myeloma cells were exposed for 2 hours to autologous IL-2–activated PBMCs and cell surface expression of CD107a on NK cells was analyzed. The assay was performed at the effector-target (E/T) ratio of 2.5:1. Significant differences, as calculated by paired Student t test, were found comparing NT versus melphalan-treated samples (P < .05). Statistical analysis on bortezomib-treated samples was not performed since 2 patients (P2 and P5) were studied. To evaluate NKG2D and DNAM-1 contribution, we performed the degranulation assay by preincubating PBMCs with the anti-NKG2D, anti–DNAM-1, or anti–MHC I neutralizing mAbs before the assay (P2 and P5).