ArticleBlood2007
WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model engrafted with healthy human stem cells transduced with C-terminus-truncated CXCR4.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- Gene therapy via CRISPR/Cas9-mediated Cxcr4 disease allele inactivation reverses leukopenia in WHIM mice.The Journal of clinical investigation · 2026Article
- CRISPR/Cas9-mediated Cxcr4 disease allele inactivation for gene therapy in a mouse model of WHIM syndrome.Blood · 2023Article
- Dynamin-2 deficiency causes age- and sex-dependent neutropenia and myelodysplasia in mice.Blood advances · 2023Article
- Reduced G protein signaling despite impaired internalization and β-arrestin recruitment in patients carrying a CXCR4Leu317fsX3 mutation causing WHIM syndrome.JCI insight · 2023Article
- Targeting CXCR4 and CD47 Receptors: An Overview of New and Old Molecules for a Biological Personalized Anticancer Therapy.International journal of molecular sciences · 2022Review
- Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer.Journal of leukocyte biology · 2021Review
- The negative charge of the 343 site is essential for maintaining physiological functions of CXCR4.BMC molecular and cell biology · 2021Article
- Low-level Cxcr4-haploinsufficient HSC engraftment is sufficient to correct leukopenia in WHIM syndrome mice.JCI insight · 2019Article
- Cxcr4-haploinsufficient bone marrow transplantation corrects leukopenia in an unconditioned WHIM syndrome model.The Journal of clinical investigation · 2018Article
- Chemokines in homeostasis and diseases.Cellular & molecular immunology · 2018Review
- Rare Genetic Blood Disease Modeling in Zebrafish.Frontiers in genetics · 2018Review
- Lymphoid differentiation of hematopoietic stem cells requires efficient Cxcr4 desensitization.The Journal of experimental medicine · 2017Article
- CXCL12 Mediates Aberrant Costimulation of B Lymphocytes in Warts, Hypogammaglobulinemia, Infections, Myelokathexis Immunodeficiency.Frontiers in immunology · 2017Article
- Neutrophils in host defense: new insights from zebrafish.Journal of leukocyte biology · 2015Review
- Article
- Chromothriptic cure of WHIM syndrome.Cell · 2015Article
- Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind.Current opinion in immunology · 2015Review
- Human Immunodeficiencies Related to Defective APC/T Cell Interaction.Frontiers in immunology · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
WHIM(warts, hypogammaglobulinemia, recurrent bacterial infection, and myelokathexis) syndrome is a rare immunodeficiency caused in many cases by autosomal dominant C-terminal truncation mutations in the chemokine receptor CXCR4. A prominent and unexplained feature of WHIM is myelokathexis (hypercellularity with apoptosis of mature myeloid cells in bone marrow and neutropenia). We transduced healthy human CD34(+) peripheral blood-mobilized stem cells (PBSCs) with retrovirus vector encoding wild-type (wt) CXCR4 or WHIM-type mutated CXCR4 and studied these cells ex vivo in culture and after engraftment in a nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse xenograft model. Neither wt CXCR4 nor mutated CXCR4 transgene expression itself enhanced apoptosis of neutrophils arising in transduced PBSC cultures even with stimulation by a CXCR4 agonist, stromal cell-derived factor-1 (SDF-1 [CXCL12]). Excess wt CXCR4 expression by transduced human PBSCs enhanced marrow engraftment, but did not affect bone marrow (BM) apoptosis or the release of transduced leukocytes into PB. However, mutated CXCR4 transgene expression further enhanced BM engraftment, but was associated with a significant increase in apoptosis of transduced cells in BM and reduced release of transduced leukocytes into PB. We conclude that increased apoptosis of mature myeloid cells in WHIM is secondary to a failure of marrow release and progression to normal myeloid cell senescence, and not a direct effect of activation of mutated CXCR4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.