Fig. 2. Plasma cells from patients diagnosed with AL amyloidosis undergo apoptosis in response to BH3 mimetics targeting BCL-2, MCL-1, and BCL-X_L. BH3 profiling correlates with ex vivo sensitivity to specific BH3 mimetics.

a Plasma cells were isolated from patient bone marrow aspirates, cultured ex vivo, and treated with BH3 mimetics. Cell death was measured by the loss of CD138⁺ cells after 24 h. b Patient samples were stratified into treatment naïve or relapsed subgroups according to their treatment status at the time of collection. Patients’ apoptotic response to BH3 mimetics indicated. c Comparison of BCL-2 dependence (apoptosis induced by ABT-199) versus MCL-1 dependence (apoptosis induced by S63845) across 31 patients that were not being treated at the time of sample collection. d–e The strength of correlation between clonal plasma cells’ apoptotic sensitivity via BH3 profiling at the time of isolation and their ex vivo chemosensitivity after 24 h ex vivo treatment were measured for d BAD BH3 peptide treatment (indicating BCL-2, BCL-X_L dependence) and ABT-263 treatment (BCL-2, BCL-X_L inhibitor), and e MS-1 peptide treatment (MCL-1 dependence) and 1 µM S63845 treatment (MCL-1 inhibitor). Spearman rho was used to test for correlation between responses to BH3 peptides and cellular sensitivity to indicated agents. f A subset of patient specimens were treated with both ABT-199 and S63845 and cell death was measured after 24 hours (n = 14). g HSA synergy analysis for combination ABT-199 and S63845 treatment. P-values were calculated using one-way ANOVA with Holm-Sidak’s adjustment for a.