title: AMD3100 synergizes with G-CSF to mobilize repopulating stem cells in Fanconi anemia knockout mice.
abstract: Fanconi anemia (FA) is a heterogeneous inherited disorder characterized by a progressive bone marrow (BM) failure and susceptibility to myeloid leukemia. Genetic correction using gene-transfer technology is one potential therapy. A major hurdle in applying this technology in FA patients is the inability of granulocyte colony-stimulating factor (G-CSF) to mobilize sufficient numbers of hematopoietic stem (HSC)/progenitor cells (HPC) from the BM to the peripheral blood. Whether the low number of CD34(+) cells is a result of BM hypoplasia or an inability of G-CSF to adequately mobilize FA HSC/HPC remains incompletely understood. Here we use competitive repopulation of lethally irradiated primary and secondary recipients to show that in two murine models of FA, AMD3100 synergizes with G-CSF resulting in a mobilization of HSC, whereas G-CSF alone fails to mobilize stem cells even in the absence of hypoplasia.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pulliam
authors.forename: M Joe
authors.initials: MJ
authors.lastname: Hobson
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Ciccone
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.forename: Edward F
authors.initials: EF
authors.lastname: Srour
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Yang
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.forename: D Wade
authors.initials: DW
authors.lastname: Clapp
mesh_terms: D000818:Animals; D001596:Benzylamines; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured / Q000187:drug effects; D003114:Colony-Forming Units Assay; D000080027:Cyclams; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005199:Fanconi Anemia / Q000235:genetics / Q000601:surgery*; D052217:Fanconi Anemia Complementation Group A Protein / Q000172:deficiency / Q000235:genetics; D052218:Fanconi Anemia Complementation Group C Protein / Q000172:deficiency / Q000235:genetics; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D036102:Peripheral Blood Stem Cell Transplantation; D011828:Radiation Chimera; D014184:Transplantation, Homologous
chemical_list: D001596:Benzylamines; D000080027:Cyclams; C120277:Fanca protein, mouse; C497652:Fancc protein, mouse; D052217:Fanconi Anemia Complementation Group A Protein; D052218:Fanconi Anemia Complementation Group C Protein; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor