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Abstract
Introduction: The chemoattractant CXCL12 (also known as stroma-derived factor-1 α) and its receptor CXCR4 (CD184) play an important role in maintaining and sustaining leukemia cells in marrow. Plerixafor, a CXCR4 antagonist, can disrupt adhesive leukemia–stroma interactions with potential to increase chemotherapy inhibition.
Areas covered: This review of the potential role of plerixafor in leukemia covers the function of the CXCL12/CXCR4 axis in normal hematopoiesis as well as studies documenting the importance of this system in leukemogenesis. The chemistry and pharmacology of plerixafor, a bicyclam CXCR4 antagonist, are discussed as well as its approved indications in stem-cell mobilization for autologous stem-cell transplantation purposes. The in vitro and murine xenograft effects of CXCR4 antagonism in acute myelogenous leukemia (AML) are covered as are clinical trials that have focused on plerixafor in various types of leukemia. Other inhibitors of the CXCL12/CXCR4 axis are also discussed as some of these are in current trials in AML.
Expert opinion: Whether inhibitors of CXCR4 will have ability to improve outcomes in leukemia remains to be seen. In any event, the concept of overcoming stroma-mediated protection from chemotherapy effects appears to have potential in this regard.
Declaration of interest
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.