Analysis of a large single institution cohort of related donors fails to detect a relation between SDF1/CXCR4 or VCAM/VLA4 genetic polymorphisms and the level of hematopoietic progenitor cell mobilization in response to G-CSF

PLoS One. 2020 Mar 5;15(3):e0228878. doi: 10.1371/journal.pone.0228878. eCollection 2020.

Abstract

We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chemokine CXCL12 / genetics*
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Integrin alpha4beta1 / genetics*
  • Living Donors
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, CXCR4 / genetics*
  • Transplantation, Homologous
  • Vascular Cell Adhesion Molecule-1 / genetics*
  • Young Adult

Substances

  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Integrin alpha4beta1
  • Receptors, CXCR4
  • Vascular Cell Adhesion Molecule-1
  • Granulocyte Colony-Stimulating Factor

Grants and funding

This work was supported by Institut Paoli-Calmettes, Inserm and by Etablissement Français du Sang and CNRS.