To determine pre-mitochondrial apoptosis restriction in these microenvironmentally activated CLL cells in vivo, we assessed the activation of Bax/Bak in CD69Pos/Neg CLL cells using an apoptosis threshold assay (ATA) following incubation of patient PBMCs with selective BH domain antagonists ex vivo (inhibitor of Bcl-2 [VEN], Mcl-1 [S63845], and Bcl-xL [A1155463]), as described in Methods. This evidence concerns the gene BAK1 and B-cell chronic lymphocytic leukemia.