AMD3100 and G-CSF Mobilize Different CD34+ Cell Populations Based on Gene and miRNA Expression

Plerixafor (AMD3100) and G-CSF mobilize peripheral blood stem cells (PBSCs) by different mechanisms. A rhesus macaque model was used to compare plerixafor and G-CSF-mobilized CD34+ cells. Three PBSC concentrates were collected from 3 macaques treated with G-CSF, plerixafor, or plerixafor plus G-CSF. CD34+ cells were isolated by immunoselection and were analyzed by global gene and micro RNA (miR) expression microarrays. Unsupervised hierarchical clustering of the gene expression data separated the CD34+ cells into three groups based on mobilization regimen. Plerixafor-mobilized cells were enriched for B cells, T cells and mast cells genes and G-CSF-mobilized cells were enriched for neutrophils, and mononuclear phagocytes (MPs) genes. Genes up-regulated in plerixafor plus G-CSF-mobilized CD34+ cells included many that were not up-regulated by either agent alone. Two hematopoietic progenitor cell miR, miR-10 and miR-126, and a dendritic cell miR, miR-155, were up-regulated in G-CSF-mobilized CD34+ cells. A pre-B cell acute lymphocytic leukemia miR, miR-143-3p, and a T cell miR, miR-143-5p, were up-regulated in plerixafor plus G-CSF-mobilized cells. The composition of CD34+ cells is dependent on the mobilization protocol. Plerixafor-mobilized CD34+ cells include more B, T, and mast cell precursors while G-CSF-mobilized cells have more neutrophil and MP precursors. Three rhesus macaques were given all three mobilization protocols and PBSCs were collected from each of these three animals. Two monkeys were given plerixafor first, one was given G-CSF first and all three were given plerixafor plus G-CSF last. This resulted in 6 samples (CD34+ and CD34- cells from each of the 3 mobilizations) from each of the 3 individual animals (biological replicates).