In this issue of Blood, Nervi and colleagues and Zeng and colleagues independently report similar findings in both in vitro and in vivo AML models, showing chemosensitization by blocking CXCR4/CXCL12 (SDF-1{alpha}:stromal cell–derived factor 1) signaling using novel CXCR4 antagonist bicyclams, namely AMD3100 (plerixafor) and AMD3465.Excerpt from the final paragraph:
Finally, while both reports open new avenues for overcoming in vivo drug resistance in AML, it is yet unclear whether durable complete remissions can ensue from this strategy. AML is indeed a very heterogenous disease, and successful eradication of leukemic stem/progenitor cells will require blocking multiple receptors/pathways ...The two articles discussed in this editorial are:
1) Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100 by Bruno Nervi and 10 co-authors, including Timothy J Ley, and John F DiPersio, Blood 2009(Jun 11); 113(24): 6206-14 [Epub 2008(Dec 2)]. [PubMed Citation].
2) Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML by Zhihong Zeng and 12 co-authors, Blood 2009(Jun 11); 113(24): 6215-24 [Epub 2008(Oct 27)]. [PubMed Citation][FriendFeed entry].
[Only the abstracts of these two articles are currently publicly accessible].
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