Fig. 4.

CD138⁺ BMA plasma cells shift their dependency to PI3K/AKT pathway with increased sensitivity to copanlisib A WB of magnetic bead selected CD138 + plasma cells from RRMM patient’s BMA after 48 h in vitro treatment with with encorafenib (ENC; 50 nM) and binimetinib (BIN; 250 nM), regorafenib alone (REG; 1μΜ), combination of the three drugs or copanlisib alone (25 nM). B Rlative protein expression of pERK, pS6, pAKT and BRAF (V600E) after quantification and normalization to actin C CD138 + viability measurement after 48 h in vitro treatment with with encorafenib (ENC; 50 nM) and binimetinib (BIN; 250 nM), regorafenib alone (REG; 1 μΜ), combination of the three drugs or copanlisib alone (25 nM). D RNA expression shows elevated PI3K/Akt pathway activation, measured as a combined z-score, throughout the course of treatment with triple MAPK inhibition therapy