In this context, we have recently demonstrated that, in normal primary T- and B-lymphocytes, as well as in CLL B-cells, JAK2 tyrosine kinase is a very upstream signaling event activated by CXCR4 and leading to the activation of the rho module of integrin affinity triggering, ultimately responsible for LFA-1 and VLA-4-mediated immediate arrest of circulating leukocytes [24, 25]. The gene discussed is JAK2; the disease is B-cell chronic lymphocytic leukemia.