Fig 7.

KPT185, KPT249, and KPT330 sensitize patient myeloma cells to doxorubicin, bortezomib, and carfilzomib. Bone marrow mononuclear cells were isolated and treated with SINE (300 nM) ± doxorubicin (2 µM), bortezomib (10 nM), carfilzomib (20 nM), or DMSO vehicle control (VC) for 20 hours. Treated cells were fluorescently labeled with antibodies against activated caspase 3, CD138, and light chain (kappa or lambda). Results for patient multiple myeloma cells (n=12 patient samples) (A-C) and patient non-myeloma cells (n=12) (D-F) are shown. Apoptosis was induced when SINE molecules were co-incubated with doxorubicin (P = 0.0004), bortezomib (P = 0.003), or carfilzomib (P = 0.002) in CD138/light-chain double-positive myeloma cell populations (A-C) but not in non-myeloma CD138/light-chain double-negative cells (P > 0.25) (D-F). This indicates that SINE may specifically inhibit neoplastic cells in MM patients.