Fig. 4

Correlations between BCL-2 dependence and multi-omics analyses were experimentally re-capitulated in cell lines. A Baseline BH3-profiling was performed for two DLBCL cell lines OCI-Ly1 and OCI-Ly3. High CytC release by BH3 peptides or mimetic drug indicates inclined dependence towards its respective anti-apoptotic protein(s) for survival (n = 3). Specific dependences as reflected on the right. B Delta CytC release between OCI-Ly3 and OCI-Ly1 (CytC release % value of OCI-Ly3 minus CytC release % value of OCI-Ly1) was calculated to reflect absolute changes in dependence to specific anti-apoptotic protein(s) for survival. Net + % indicates relative increased or better dependence and net—% suggests relative decreased dependence (n = 3). C Western blot analysis showing protein expression levels of BIM-xL, L, S, phosphor-IKK, total IKK, BAX, BAK and respective β-Actin(s) of OCI-Ly1 and OCI-Ly3. D Mitochondrial respiration or OXPHOS measurement between OCI-Ly1 and OCI-Ly3. Asterisks indicate addition of oligomycin (*), FCCP (**), antimycin-A/rotenone (***) to indicate basal and maximal respirations. Representative graph is shown here (n = 3). E Mitosox staining was measured and quantified between OCI-Ly1 and OCI-Ly3 (n = 3). Unpaired t-test was used. F, G Cell viability by CellTiter-Glo® was measured between OCI-Ly1 and OCI-Ly3 following 48-h treatment with increasing doses of ABT199 (VEN) (n = 4), ibrutinib (n = 3), etoposide (n = 4) or doxorubicin (n = 4)