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.
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.
S M
SM
Watt
S P
SP
Forde
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