Effects of AMD3100 on transmigration and survival of acute myelogenous leukemia cells.
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.
Liesveld
Jane L
JL
James P Wilmot Cancer Center and the Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA. jane_liesveld@urmc.rochester.edu
Bechelli
Jeremy
J
Rosell
Karen
K
Lu
Chaohui
C
Bridger
Gary
G
Phillips
Gordon
G
Abboud
Camille N
CN
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D001596:Benzylamines; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors; D018920:Coculture Techniques; D003470:Culture Media; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010766:Phosphorylation
D018952:Antigens, CD34; D001596:Benzylamines; D054377:Chemokine CXCL12; D003470:Culture Media; D000080027:Cyclams; D006571:Heterocyclic Compounds; C088327:plerixafor