The possibility that leukemic B cells contribute directly to bone impairment has been explored in preclinical studies demonstrating a critical role of the receptor activator of the nuclear factor κB ligand (RANKL)-osteoprotegerin(OPG)/receptor activator of the nuclear factor κB (RANK) receptor axis in causing B-ALL cell-mediated bone damage [24,25]. This evidence concerns the gene TNFSF11 and acute lymphoblastic leukemia.