TGR-1202 and carfilzomib synergistically inhibit survival of lymphoma and leukemia cell lines and primary cells. The following drugs were studied: Bz, bortezomib; Cfz, carfilzomib; IB, Ide + Bz; Ide, idelalisib; TC, TG + Cfz; TG, TGR-1202. (A) EOB values calculated for 4 combinations of treatment in the DLBCL cell line LY10. Cells were treated for 24 hours with the indicated drugs and concentrations as single agents and in combinations. Viable cells were quantitated by the Cell-Titer Glo assay (Promega). EOB values above 0 indicate synergy. (B) Cell lines representing different hematological malignancies were treated for 48 hours. The y- and x-axes indicate the observed and expected percentage of inhibition, respectively. The expected inhibition was calculated using the Bliss model. The diagonal line indicates the line of additivism. Synergy was demonstrated by observed inhibition in excess of the expected inhibition. (C) Primary lymphoma and leukemia cells were isolated by Ficoll gradient separation from 3 patients with SLL, CLL, and MCL respectively. The SLL cells were from pleural fluid, and the CLL and MCL cells were from peripheral blood. Top panel, The results combining Ide and Bz; bottom panel, TG and Cfz. Ide and TG were given at 2.5, 5, and 7.5 μM, and their effects on viability were presented by the unconnected “×” markers. All of the other treatments were as indicated on the graphs. Viability was determined after 48 hours of treatment. (D) LY10 and LY7 cell lines were treated as indicated for 24 hours and processed for western blot. For LY7, TG and Ide were at 3 μM, and Bz and Cfz were at 5 nM; for LY10, TG and Ide were at 3 μM, and Bz and Cfz were at 2 nM. neg, negative control; PARP, poly (ADP-ribose) polymerase.