Different groups reported that malignant cells that recently interacted in vivo with the supportive microenvironment of lymphoid tissues (9, 10), or those that were cultured in vitro with different signals that mimic microenvironment stimuli (11–15), show an increased expression of BCL-XL and MCL-1 and are less sensitive to venetoclax compared to quiescent or unstimulated CLL cells. This evidence concerns the gene MCL1 and B-cell chronic lymphocytic leukemia.