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SDF-1 and CXCR4 in normal and malignant hematopoiesis J. Juarez and L. Bendall Westmead Institute for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia Offprint requests to: Dr. Linda Bendall, Westmead Institute for Cancer Research, Westmead Millennium Institute, Westmead, NSW, 2145, Australia. Fax: 61-2-98459102. e-mail: linda.bendall@wmi.usyd.edu.au
Summary. 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. Histol. Histopathol. 19, 299-309 (2004) Key words: SDF-1,
CXCR4, Leukemia, Hematopoiesis |