SDF-1 and CXCR4 in normal and malignant hematopoiesis.
Over recent years it has become apparent that the chemokine SDF-1 and its receptor CXCR4 play pivotal roles in normal hematopoiesis. They are essential for the normal ontogeny of hematopoiesis during embryogenesis and continue to play a key role in retaining hematopoietic progenitors within the bone marrow microenvironment in the adult. As a result of this role disruption of SDF-1/CXCR4 interactions results in mobilization of hematopoietic progenitors and standard mobilization protocols disrupt this axis. Similarly SDF-1/CXCR4 interactions are required for homing and engraftment of hematopoietic stem cells during transplantation. SDF-1 regulates the localisation of leukemic cells and like their normal counterparts most leukemic cells respond to SDF-1 with increased adhesion, survival and proliferation. However in some instances leukemic cell responses to SDF-1 can be disregulated, the impact of which on the progression of disease in not known. In this review we discuss the pleiotropic roles of SDF-1/CXCR4 interactions in human hematopoietic stem cell ontogeny, bone marrow homing and engraftment, mobilization and how these interactions impact on malignant hematopoiesis.
Juarez
J
J
Westmead Institute for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
Bendall
L
L
D000818:Animals; D001853:Bone Marrow; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000503:physiopathology; D019718:Receptors, CXCR4 / Q000502:physiology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4