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

摘要

Data clustering as assessed by k-means is shown for MCL1 and BCL2 inhibitors induced cell death in 60 patients (  = 1000 initiations of algorithm). Clusters for MCL1 inhibitor response ( 12.5, 25 and 50 nM) with increasing sensitivity from 1 to 4. Patient distribution according to disease status for MCL1 sensitivity clustering. Statistical analysis was done using Fisher’s exact test. Clusters for BCL2 inhibitor response (venetoclax 100, 300, and 1000 nM) with increasing sensitivity from 1 to 3. Patient distribution according to disease status for BCL2 sensitivity clustering. Primary MM cells sensitivity to MCL1 inhibitor (50 nM) according to 1q gain (  = 27). 1q amplification was detected by FISH analysis. Statistical analysis was done using Mann–Whitney test,  = 0.64.