AMD3100 and G-CSF Mobilize Different CD34+ Cell Populations Based on Gene and miRNA Expression. 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. Overall design: 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).