Our mechanistic dissection of the AXIN2 VCM not only allowed us to tackle fundamental questions of how gene activation and VCM formation are controlled, but it also allowed us to provide insights into the flow of molecular information from non-coding variant to likely phenotype (in this case, CLL susceptibility and disease progression, which have already been suggested to also be influenced by regulatory variation61). Here, AXIN2 is linked to B-cell chronic lymphocytic leukemia.