Journal
CURRENT OPINION IN HEMATOLOGY
Volume 16, Issue 1, Pages 20-26Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0b013e32831ac557
Keywords
apoptosis; B-cell lymphopenia; G-protein coupled receptor; G-protein coupled receptor kinase 3; human papilloma virus; hypogammaglobulinemia; myelokathexis; neutropenia; stromal cell-derived factor 1; warts
Categories
Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI000988, ZIAAI000645] Funding Source: NIH RePORTER
- Intramural NIH HHS [Z01 AI000645-16] Funding Source: Medline
Ask authors/readers for more resources
Purpose of review Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is characterized by susceptibility to human papilloma virus infection-induced warts and carcinomas; neutropenia, B-cell lymphopenia and hypogammaglobulinema-related infections; and bone marrow myelokathexis (myeloid hyperplasia with apoptosis). The purpose of this report is to review new findings about WHIM. Recent findings Most WHIM patients have heterozygous C-terminus deletion mutations of the intracellular carboxy terminus of the chemokine receptor CXCR4. WHIM leukocytes have enhanced responses to CXCL12, the cognate ligand of CXCR4. Enhanced activity of CXCR4 delays release of mature neutrophils from bone marrow, resulting in neutropenia and apoptosis of mature neutrophils retained in the marrow. Finding two patients with WHIM who do not have detectable mutations of CXCR4 but whose cells are hyperresponsive to CXCL12 raises the possibility that there is more than one genetic basis for WHIM. One patient had low levels of G-protein receptor kinase 3, and the functional hyperactivity response to CXCL12 was corrected by forced gene transfer-mediated overexpression of G-protein receptor kinase 3, implicating defects in function of this protein as a potential alternate genetic cause of WHIM. Summary Subjects reviewed include clinical presentation, diagnosis, and treatment of WHIM and advances in understanding the genetic basis of WHIM.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available