Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF) mobilize different CD34+ cell populations based on global gene and microRNA expression signatures.
Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF) mobilize peripheral blood stem cells by different mechanisms. A rhesus macaque model was used to compare plerixafor and G-CSF-mobilized CD34(+) cells. Three peripheral blood stem cell 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 microRNA (miR) expression microarrays. Unsupervised hierarchical clustering of the gene expression data separated the CD34(+) cells into 3 groups based on mobilization regimen. Plerixafor-mobilized cells were enriched for B cells, T cells, and mast cell genes, and G-CSF-mobilized cells were enriched for neutrophils and mononuclear phagocyte 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, whereas G-CSF-mobilized cells have more neutrophil and mononuclear phagocyte precursors.
Donahue
Robert E
RE
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Jin
Ping
P
Bonifacino
Aylin C
AC
Metzger
Mark E
ME
Ren
Jiaqiang
J
Wang
Ena
E
Stroncek
David F
DF
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism*; D001596:Benzylamines; D015415:Biomarkers / Q000378:metabolism; D000080027:Cyclams; D004338:Drug Combinations; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D008253:Macaca mulatta; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D019380:Anti-HIV Agents; D018952:Antigens, CD34; D001596:Benzylamines; D015415:Biomarkers; D000080027:Cyclams; D004338:Drug Combinations; D006571:Heterocyclic Compounds; D035683:MicroRNAs; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor