Enhancement of stem cell engraftment on a WHIM
Hal E. Broxmeyer
Hal E. Broxmeyer
Published June 25, 2018
Citation Information: J Clin Invest. 2018;128(8):3240-3242. https://doi.org/10.1172/JCI121857.
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Commentary

Enhancement of stem cell engraftment on a WHIM

Abstract

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a genetic autoimmune disorder that results from gain-of-function mutations in the gene encoding chemokine receptor CXCR4. A previous study characterized a patient with WHIM who underwent a chromothriptic event that resulted in spontaneous deletion of the WHIM allele in a single hematopoietic stem cell and subsequent cure of the disease. In this issue of the JCI, Gao et al. extend this work and show that Cxcl4-haplosufficient bone marrow has a selective advantage for long-term engraftment in murine WHIM models. Moreover, successful engraftment occurred without prior conditioning of recipients. Together, these results have important implications for improving hematopoietic stem/progenitor cell transplant not only for patients with WHIM but also for all patients who may require the procedure.

Authors

Hal E. Broxmeyer

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Figure 1

Modulation of CXCR4 and associated pathways may enhance HSC engraftment.

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Modulation of CXCR4 and associated pathways may enhance HSC engraftment....
(A) Summary of some findings of Gao et al. (2). Engraftment of WT (Cxcr4+/+), hemizygous (Cxcr4+/o), or WHIM (Cxcr4+/w) donor cells in either lethally irradiated Cxcr4+/+ mice or in unconditioned Cxcr4+/+ or Cxcr4+/w recipients. Hemizygous Cxcr4 cells have markedly increased engraftment compared with cells from WT or WHIM mice. (B) Several additional possibilities to enhance engraftment of HSCs in the context of WHIM and other nonmalignant or malignant disorders. These include HSC collection under hypoxic conditions and strategies to modify CXCR4, CXC12, and DPP4 in the bone marrow microenvironment of recipients. ↑, denotes engraftment, ↑↑, greater engraftment, ↑↑↑, even greater engraftment, and X, no engraftment. Details are provided in the text of this commentary.