Conditioning response to granulocyte colony-stimulating factor via the dipeptidyl peptidase IV-adenosine deaminase complex.
G-CSF is routinely used to mobilize hematopoietic stem cells (HSCs) from bone marrow (BM) into peripheral blood before aphaeresis, but HSC harvesting can be suboptimal. On the other hand, transplanted HSCs sometimes fail to engraft a recipient BM microenvironment when G-CSF is used after transplantation, as pushing-CSF will push HSCs away from marrow. So, G-CSF action needs to be potentiated by other drugs. Marrow stromal cells establish a local CXCL12 concentration gradient that is the primary homing signal for HSCs. Pharmacological interventions that modify this gradient, therefore, have potential to help HSC mobilization (by decreasing CXCL12) and engraftment (by increasing CXCL12). CXCL12 inactivation is primarily mediated by dipeptidyl peptidase-IV. We review here the currently available drugs affecting this enzyme that could be used in the clinic to achieve phase-specific help for G-CSF.
Focosi
Daniele
D
Division of Hematology, Azienda Ospedaliera Santa Chiara, University of Pisa, via Roma 56, 56100 Pisa, Italy. dfocosi@fin.org
Kast
Richard Eric
RE
Galimberti
Sara
S
Petrini
Mario
M
D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D001781:Blood Component Removal; D001854:Bone Marrow Cells / Q000502:physiology; D054377:Chemokine CXCL12 / Q000502:physiology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000502:physiology
D054377:Chemokine CXCL12; D008222:Lymphokines; D019718:Receptors, CXCR4; C032916:glia cell stimulating factor; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase