In vitro reponse to venetoclax in patient samples collected pre- and postprogression on venetoclax. Pre- and postprogression time point PBMC samples (refer to the classification column of supplemental Table 1) were treated with escalating concentrations of venetoclax (A-C) for 24 hours. (A) Representation of survival as analyzed using CellTiter-Glo and the line connects matched pre- and postprogression samples for each patient. Data from panel A was split as patients with and without loss(8p) (B) and with and without gain(1q) (C). The x-axis represents the ratio of surviving cells in postprogression/pretreatment samples. (D) Pre- and postprogression samples were treated with the MCL1 inhibitor S63485 for 24 hours and surviving cells were estimated with CellTiter-Glo. Patients with and without gain(1q) were compared. The x-axis represents the ratio of surviving pre/postprogression samples. (E) Pre- and postprogression samples were treated with 33.3 nM S63485 for 24 hours in combination with escalating concentrations of venetoclax, and surviving cells were determined by CellTiter-Glo. The line connects matched pre- and postprogression samples for each patient. Patients with and without gain(1q) were compared. The x-axis represents cell survival upon treatment with various drugs.