The minor transcriptional differences between M-CLL-S and M-CLL-NS were surprising, given the association between signalling capacity and patient outcomes [8], however, this may reflect a cohort size that was insufficiently powered or factors such as tumour microenvironmental interaction, antigen driven/autonomous signalling, IGHV gene usage or somatic variants, may have limited our ability to detect in vivo BCR engagement induced anergic transcriptional signatures. This evidence concerns the gene BCR and B-cell chronic lymphocytic leukemia.