BCR and B-cell chronic lymphocytic leukemia: In patients, CLL cells have elevated BTK expression (36) and pBTK levels compared to healthy B cells (28), as well as lower expression of surface IgM (sIgM) (37) which is additional evidence for BCR stimulation in vivo, as sIgM expression in CLL cells is downregulated after antigen stimulation which is reversed during circulation in the PB (38).