In light of the HPV-pathogenesis associated with the WHIM syndrome, it can be extrapolated that dysfunction of CXCR4 might be acquired from genetic errors accumulated during the multistep process of HPV-induced neoplasia, as demonstrated by the somatic WHIM-like CXCR4 mutations reported in Waldenström macroglobulinemia [70] or the anomalies in the effectors of the CXCL12/CXCR4-signaling pathway reported in patients with GATA2-deficiency [71–73]. This evidence concerns the gene CXCL12 and Waldenstrom macroglobulinemia.