It is interesting to note that dampening of the ADP response, that occurs during CLL disease progression, is attributable exclusively to selective disruption of the negative regulatory pathways (e.g. SIRPα, HDAC7, ship1) rather than the activating pathways (e.g. SYK, BTK, PI3K, SLAMF7). This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.