RNA-seq of S63845 sensitive and resistant myeloma cell lines.

We performed RNA-seq analysis of in-house generated S63845 sensitive and resistant myeloma cell lines OPM-2 and KMS-12-BM in order to define common events in the acquisition of MCL-1 inhibitor resistance. Our results, however, point to the occurrence of cell line specific, heterogeneous paths to resistance as no common differences were observed. Subsequent experiments rather revealed that the binding kinetics of BH3 family members are a major driver of MCL-1 inhibitor resistance and that individual shifts during the establishment of resistance dependent on the baseline BH3 family profile. Overall design: Comparison of myeloma cell line models with acquired S63845 resistance and their sensitive (long-term culture) control. RNA-seq was performed in untreated cells.