|DNA Change (Coding Nucleotide)
CXCR4 is a chemokine receptor which has been shown to mutated in approximately 25-30% of patients with Waldenstrom's Macroglobulinemia(WM). The mutations are nonsense and frameshift mutations in the carboxy terminus of the protein. Similar mutations are found in WHIM (Warts, Hypogammaglobulinemia, Infection and Myelokathexis) syndrome, a rare, autsomal dominant genetic disorder. These mutations in the carboxy terminal tail lead to impaired receptor desensitization and internalization, resulting in enhanced receptor activation and increased expression. Almost all WM patients with mutation of CXCR4 also carry the MYD88 L265P mutation. Mutations in CXCR4 appear to be mutually exclusive of mutations in CD79A/CD79B. Patients with CXCR4 mutations may be candidates for targeted therapy since CXCR4 antagonists have been used in patients with WHIM syndrome. The presence of CXCR4 mutations may affect response to Ibrutinib therapy according to some studies.