Effects of AMD3100 on transmigration and survival of acute myelogenous leukemia cells.

ABSTRACT

Acute myelogenous leukaemia (AML) blasts transmigrate in response to SDF-1alpha. AMD3100, a novel bicyclam molecule which inhibits stromal-derived factor (SDF)-1alpha/CXCR4 interactions, inhibited the transmigration of AML blasts and inhibited outgrowth of leukemia colony forming units. AMD3100 did not abrogate stroma-mediated protection from cytarabine-mediated apoptosis, except in the case of one promyelocytic leukemic sample tested, and it did not influence adhesion of blasts to endothelial monolayers. When AML blasts were pretreated with AMD3100, the positive effects of SDF-1alpha on NOD/SCID engraftment were diminished. This work confirms that AML is influenced by the SDF-1alpha/CXCR4 axis and demonstrates that disruption of this axis by the bicyclam AMD3100 can influence AML microenvironmental interactions.