The central role of the chemokine receptor, CXCR4, in haemopoietic stem cell transplantation: will CXCR4 antagonists contribute to the treatment of blood disorders?
Recent clinical trials have used CXCR4 antagonists for the rapid mobilization of CD34(+) haemopoietic stem/progenitor cells (HSC/HPC) from the bone marrow to the blood in patients refractory to granulocyte-colony-stimulating factor (G-CSF). These antagonists not only mobilize non-cycling cells with a higher proportion of repopulating cells, but also enhance CD34(+) cell mobilization when used in combination with G-CSF. Here, we review the importance of CXCR4 and its ligand CXCL12 in haemopoiesis, and the potential roles of CXCR4 antagonists in the clinical HSC transplant setting.
Watt
S M
SM
Stem Cells and Immunotherapies, NHS Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, UK and Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, UK.
Forde
S P
SP
D000595:Amino Acid Sequence; D054377:Chemokine CXCL12 / Q000502:physiology; D002986:Clinical Trials as Topic; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006402:Hematologic Diseases / Q000628:therapy*; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054387:Receptors, CXCR / Q000737:chemistry / Q000235:genetics; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid
C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor