Sub-clonal upregulation of alternative BCL2 family members, BCL-XL and MCL1, have also been identified.318,321 This has been associated with copy number gains or increased NF-κB signaling which drives protein expression.321,322 Additionally, acquired variants of the effector BAX or loss of BAX protein have been reported in the myeloid compartment of venetoclax-resistant AML and CLL patients.323,324. This evidence concerns the gene MCL1 and acute myeloid leukemia.