title: Effective mobilization of hematopoietic progenitor cells in G-CSF mobilization defective CD26-/- mice through AMD3100-induced disruption of the CXCL12-CXCR4 axis.
abstract: OBJECTIVE
  We previously reported that inhibition or loss of CD26 (DPPIV/dipeptidylpeptidase IV) results in a defect in normal mobilization of hematopoietic stem and progenitor cells induced by granulocyte-colony stimulating factor (G-CSF). This suggests that CD26 is a necessary component of the mobilization pathway. Our goal in this study was to determine whether mobilization can be induced by the CXCR4 antagonist AMD3100 in mice lacking CD26 (CD26(-/-)).
  
  
  METHODS
  Ten week old CD26(-/-) and C57BL/6 mice received a subcutaneous injection of AMD3100. One hour post-injection the mice were euthanized and peripheral blood and bone marrow were collected and evaluated.
  
  
  RESULTS
  AMD3100 mobilizes hematopoietic progenitors into the peripheral blood of CD26(-/-) and mice.
  
  
  CONCLUSIONS
  Our finding that AMD3100 rapidly mobilizes hematopoietic progenitor cells from the bone marrow into the periphery in CD26-deficient transgenic mice that otherwise exhibit a mobilization defect in response to G-CSF suggests that: (1) CD26 is downstream of G-CSF but upstream of the CXCL12-CXCR4 axis and (2) AMD3100 can be used as a single agent to mobilize hematopoietic stem and progenitor cells in normal donors or patients that have an intrinsic defect in their response to G-CSF treatment. Stem cell transplants are often the only curative treatment in some cancer patients. The ability to perform the transplantation and its success is dependent on the ability to mobilize adequate numbers of hematopoietic progenitor cells. The use of AMD3100 as a single agent would give patients or donors an additional option for a successful stem cell transplant.
authors.affiliation: Sections of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Rush University Medical Center, 1725 W. Harrison Street, Chicago, IL 60612, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Paganessi
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Walker
authors.forename: Lydia Luy
authors.initials: LL
authors.lastname: Tan
authors.forename: Isaac
authors.initials: I
authors.lastname: Holmes
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rich
authors.forename: Henry C
authors.initials: HC
authors.lastname: Fung
authors.forename: Kent W
authors.initials: KW
authors.lastname: Christopherson
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D000080027:Cyclams; D018819:Dipeptidyl Peptidase 4; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D001596:Benzylamines; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; D018819:Dipeptidyl Peptidase 4; C088327:plerixafor