The distinct drug response phenotype of trisomy 12 in CLL implies amplification of BCR signaling as the mechanism underlying this driver mutation, a finding that would explain short progression-free survival (54), high p-ERK levels (53), the different response pattern to ibrutinib (55), and the characteristic incidence of trisomy 12 in B cell malignancies. Here, BCR is linked to B-cell chronic lymphocytic leukemia.