Effect of the drug combinations brentuximab-vedotin + PKC412 on proliferation of neoplastic MCs. (A) HMC-1.1 cells, HMC-1.2 cells, MCPV-1.1 cells, MCPV-1.4 cells, and C2 cells were incubated in control medium, brentuximab-vedotin (0.1-35 µg/mL, light gray symbols), PKC412 (1-350 nM, dark gray symbols), or a combination of both drugs at fixed ratio of drug concentration (black symbols) at 37°C for 96 hours. After incubation, ³H-thymidine uptake was measured. Results are expressed as percentage of control and show 1 typical experiment for each cell line. Almost identical results were obtained in at least 1 independent experiment in each cell line using the same drug concentrations and drug combination. (B) MCPV-1.1 cells were incubated in control medium (Co), brentuximab-vedotin (100 µg/mL), PKC412 (2 µM), or a combination of both drugs (same concentrations) at 37°C for 1 hour. Then, cells were washed and injected into the tail vein of NSG mice (3 × 10⁶ cells per mouse; 4 mice per group). After 4 weeks, mice were sacrificed and MCPV-1.1 repopulation was measured by determining the percentage of CD45⁺/CD117⁺ cells in mouse BM samples by flow cytometry. Results represent engraftment as percentage of control. *P < .05.