Fig. 6: BCLXL contributes to the resistance to the S63845/venetoclax combination. | Cell Death & Disease

Fig. 6: BCLXL contributes to the resistance to the S63845/venetoclax combination.

From: Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes

Fig. 6

a Correlation of BCLXL expression and the response to the combination of BCL2 and MCL1 inhibitors. Total RNA was obtained from purified CD138+ myeloma cells from 29 samples and the expression of BCLXL was analyzed by DGE seq. Log2 normalized BCLXL mRNA counts were plotted against the percentage of cell death induced by the BCL2 and MCL1 inhibitor combination. Spearman correlation is indicated. b KMM1 and LP1cells were transfected during 24 h with control cDNA (YFP) or BCLXL cDNA (YFP-BCLXL) followed by 24 h of S63845 (50 nM) and/or venetoclax (100 nM) treatment. Cell death was assessed in YFP positive cells by Annexin V staining. Results represent the mean ± SD of five independent experiments, (*p < 0.05). Mann–Whitney test was used for statistical analysis. Overexpression of YFP and YFP-BCLXL was validated by immunoblotting. c Transfection of KMM1 and LP1 cells with scramble or BCLXL siRNA for 48 h followed by 24 h of S63845 (12.5 nM) and/or venetoclax (100 nM) treatment. Cell death was assessed by Annexin V staining. Results represent the mean ± SD of five independent experiments. Mann–Whitney test was used for statistical analysis (*p < 0.05). Silencing efficacy was validated by immunoblotting.

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