Basal levels of MCL1 and its binding partners contribute to a higher sensitivity to MCL1 inhibitors in uveal vs cutaneous melanomas

The two subtypes of melanomas, uveal (UM) and cutaneous (CM), originate from melanocyte transformation, but differ in their genetic etiology and signaling pathways. MCL1 and BCL2, the anti-apoptotic members of the BCL2 family, induce anti-cancer treatment resistance. Here, we evaluate their basal levels and role in inducing response to MCL1 inhibitor (MCL1i) in CM and UM. We used in vitro assays (viability, immunoblot and shRNA), and bioinformatics analyses of the TCGA database. UM cell lines have higher BCL2 and lower MCL1 protein expressions compared to CM.