Blocking anti-RANKL antibodies, which disrupt the RANKL–RANK interaction, thereby prevents prosurvival programs, inhibiting not only the survival of RANKK240E transgenic CLL cells, but also TCL1 transgenic CLL cells, human CLL cell lines, and primary patient samples both in vitro and in vivo. This evidence concerns the gene TNFSF11 and B-cell chronic lymphocytic leukemia.