The WHIM syndrome features susceptibility to human Papillomavirus 
infection-induced warts and carcinomas, hypogammaglobulinemia, recurrent 
bacterial infections, B and T-cell lymphopenia, and neutropenia associated with 
retention of senescent neutrophils in the bone marrow (i.e. myelokathexis). This 
rare disorder is mostly linked to inherited heterozygous autosomal dominant 
mutations in the gene encoding CXCR4, a G protein coupled receptor with a unique 
ligand, the chemokine CXCL12/SDF-1. Some individuals who have full clinical 
forms of the syndrome carry a wild type CXCR4 gene. In spite of this genetic 
heterogeneity, leukocytes from WHIM patients share in common dysfunctions of the 
CXCR4-mediated signaling pathway upon exposure to CXCL12. Dysfunctions are 
characterized by impaired desensitization and receptor internalization, which 
are associated with enhanced responses to the chemokine. Our increasing 
understanding of the mechanisms that account for the aberrant 
CXCL12/CXCR4-mediated responses is beginning to provide insight into the 
pathogenesis of the disorder. As a result we can expect to identify markers of 
the WHIM syndrome, as well as other disorders with WHIM-like features that are 
associated with dysfunctions of the CXCL12/CXCR4 axis.