Plerixafor (AMD3100) induces prolonged mobilization of acute lymphoblastic leukemia cells and increases the proportion of cycling cells in the blood in mice
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Published:25th Mar 2020
Source: Experimental Hematology
The CXCR4 antagonist Plerixafor (AMD3100) induces the rapid mobilization of hematopoietic stem and progenitor cells into the blood in mice and humans. AMD3100 similarly induces the mobilization of human acute lymphoblastic leukemia (ALL) cells into the blood in mice. In this study, the temporal response of pre-B ALL cells to AMD3100 was compared to that of normal hematopoietic progenitor cells (HPC) using a NOD/SCID xenograft model of ALL and BALB/c mice respectively. ALL cells remained in the circulation up to 6 hours post AMD3100 administration, by which time normal HPC were no longer detectable. AMD3100 also increased the proportion of actively cycling ALL cells in the peripheral blood. Together these data suggest that ALL cells may be more sensitive to the effects of BM disruption than normal progenitors. Using the NOD/SCID xenograft model we demonstrated that AMD3100 increased the efficacy of the cell cycle specific drug vincristine, resulting in reduced disease levels in the blood and spleens of animals over three weeks and extended the survival of NOD/SCID mice with ALL. These data demonstrate that mobilizing agents may increase the therapeutic effect of cell cycle dependent chemotherapeutic agents.