Cytokines and hematopoietic stem cell mobilization.
Hematopoietic stem cell transplantation (HSCT) has become the standard of care for the treatment of many hematologic malignancies, chemotherapy sensitive relapsed acute leukemias or lymphomas, multiple myeloma; and for some non-malignant diseases such as aplastic anemia and immunodeficient states. The hematopoietic stem cell (HSC) resides in the bone marrow (BM). A number of chemokines and cytokines have been shown in vivo and in clinical trials to enhance trafficking of HSC into the peripheral blood. This process, termed stem cell mobilization, results in the collection of HSC via apheresis for both autologous and allogeneic transplantation. Enhanced understanding of HSC biology, processes involved in HSC microenvironmental interactions and the critical ligands, receptors and cellular proteases involved in HSC homing and mobilization, with an emphasis on G-CSF induced HSC mobilization, form the basis of this review. We will describe the key features and dynamic processes involved in HSC mobilization and focus on the key ligand-receptor pairs including CXCR4/SDF1, VLA4/VCAM1, CD62L/PSGL, CD44/HA, and Kit/KL. In addition we will describe food and drug administration (FDA) approved and agents currently in clinical development for enhancing HSC mobilization and transplantation outcomes.
Nervi
Bruno
B
Division of Oncology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Link
Dan C
DC
DiPersio
John F
JF
D000818:Animals; D001596:Benzylamines; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D000080027:Cyclams; D016207:Cytokines / Q000378:metabolism*; D004358:Drug Therapy; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D010281:Parathyroid Hormone / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010641:Phenotype; D011092:Polyethylene Glycols; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D023063:Receptors, Interleukin-8B; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology; D019089:Stem Cell Factor / Q000378:metabolism
D001596:Benzylamines; C515255:CXCL12 protein, human; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000080027:Cyclams; D016207:Cytokines; D006571:Heterocyclic Compounds; C524898:PLAUR protein, human; D010281:Parathyroid Hormone; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019382:Human Growth Hormone; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D010447:Peptide Hydrolases; D000069585:Filgrastim; C088327:plerixafor