The mobilization of primitive hemopoietic progenitors into the peripheral blood.
There is considerable interest in the use of peripheral blood progenitor cells (PBPC) for hemopoietic rescue following high dose chemotherapy. Current regimens mobilize CD34+ with variable efficacy and there remains considerable empiricism in the design of these regimens. Some involve myelosuppression, some the administration of various cytokines alone or in combination, while a combination of chemotherapy and cytokines is employed in others. Certain protocols result in mobilization within one week while in others, maximal PBPC levels occur only after several weeks. Thus, procedures required for optimal mobilization of PBPC remain to be defined. An understanding of the mechanisms responsible for mobilization may lead to the development of improved mobilization strategies. Herein we review data that explore the mechanisms involved in the mobilization of PBPC in man. These data demonstrate that mobilization is associated with marked changes in the expression and function of cell adhesion molecules (CAMs) on hemopoietic progenitor cells (HPC), suggesting that the release of HPC into the blood involves a perturbation of the adhesive interactions between these cells and the marrow stroma that, in steady-state conditions, serve to restrict HPC to the bone marrow. Downregulation of c-kit is invariably associated with successful mobilization which, when combined with data from in vitro studies, implies a key role for stem cell factor (SCF) as an orchestrator of mobilization.
Simmons
P J
PJ
Division of Haematology, Hanson Centre for Cancer Research, Villejuif, France.
Leavesley
D I
DI
Levesque
J P
JP
Swart
B W
BW
Haylock
D N
DN
To
L B
LB
Ashman
L K
LK
Juttner
C A
CA
D000818:Animals; D001773:Blood Cells / Q000166:cytology* / Q000502:physiology; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement; D016207:Cytokines / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D016184:Receptors, Colony-Stimulating Factor / Q000502:physiology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases