The combination of perifosine and bortezomib induces a decrease in proliferation and survival in WM tumor cells. (A) Normalized isobologram produced by Calcusyn software. BCWM.1 cells were cultured with either perifosine (5 μM and 10 μM), bortezomib (5 nM and 10 nM), or the combination. The table shows affected fractions and combination indices. Cytotoxicity was assessed using MTT assay. (B) Cytotoxicity induced with several agents known in WM disease therapy. Combination indices (CI) and fractions affected (FA) produced by Calcusyn software. BCWM.1 cells were cultured with the following agents: fludarabine (1 and 5 μg/mL), melphalan (1 μM and 5 μM), and doxorubicin (0.1 nM and 0.5 nM) in combination with perifosine (5 μM and 10 μM) for 48 hours. (C) Cytotoxicity was assessed on several IgM-secreting cell lines, MEC-1 (■), WM-WSU (Δ), and RL (x). Cells were cultured with either perifosine (10 μM), bortezomib (5 nM and 10 nM), or the combination for 48 hours. (D) Freshly isolated BM CD19+ samples from 3 patients with WM treated with the combination of perifosine (10 μM), bortezomib (5 nM and 10 nM), and the combination for 48 hours. Data represent mean plus or minus SD of triplicate experiments.