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Blood, 11 June 2009, Vol. 113, No. 24, pp. 6206-6214. Prepublished online as a Blood First Edition Paper on December 2, 2008; DOI 10.1182/blood-2008-06-162123. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-162123v1 113/24/6206    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nervi, B. Articles by DiPersio, J. F Search for Related Content PubMed PubMed Citation Articles by Nervi, B. Articles by DiPersio, J. F Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 10, 2008 Accepted November 11, 2008 Chemosensitization of AML following mobilization by the CXCR4 antagonist AMD3100 Bruno Nervi, Pablo Ramirez, Michael P Rettig, Geoffrey L Uy, Matthew S Holt, Julie K Ritchey, Julie L Prior, David Piwnica-Worms, Gary Bridger, Timothy J Ley, and John F DiPersio* Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO, United States Genzyme Corporation, Cambridge, MA, United States * Corresponding author; email: jdipersi{at}im.wustl.edu. The CXCR4-SDF-1 axis plays a central role in the trafficking and retention of normal and malignant stem cells in the bone marrow (BM) microenvironment. Here, we utilized a mouse model of acute promyelocytic leukemia (APL) and a small molecule competitive antagonist of CXCR4, AMD3100, to examine the interaction of mouse APL cells with the BM microenvironment. APL cells from a murine cathepsin G-PML-RAR knock-in mouse were genetically modified with firefly luciferase (APLluc) to allow tracking by bioluminescence imaging. Co-culture of APLluc( cells with M2-10B4 stromal cells protected the leukemia cells from chemotherapy-induced apoptosis in vitro. Upon injection into syngeneic recipients, APLluc cells rapidly migrated to the BM followed by egress to the spleen then to the peripheral blood with death due to leukostasis by day 15. Administration of AMD3100 to leukemic mice induced a 1.6-fold increase in total leukocytes and a 9-fold increase of circulating APL blast counts which peak at 3 hours and return to baseline by 12 hours. Treatment of leukemic mice with chemotherapy plus AMD3100 resulted in decreased tumor burden and improved overall survival compared to mice treated with chemotherapy alone. These studies provide a proof-of-principle for directing therapy to the critical tethers that promote AML-niche interactions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Priming reloaded? Michael Heuser, Florian Kuchenbauer, Bob Argiropoulos, Sanja Sekulovic, Malina Leung, Marcin Stasiak, Arnold Ganser, and R. Keith Humphries Blood 2009 114: 925-926. [Full Text] [PDF] Response: Sensitization initiated Abdel Kareem Azab and Irene M. Ghobrial Blood 2009 114: 926-927. [Full Text] [PDF] Another nail in the AML coffin Camille N. Abboud Blood 2009 113: 6045-6046. [Full Text] [PDF] This article has been cited by other articles: A. V. Kurtova, K. Balakrishnan, R. Chen, W. Ding, S. Schnabl, M. P. Quiroga, M. Sivina, W. G. Wierda, Z. Estrov, M. J. Keating, et al. Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance Blood, November 12, 2009; 114(20): 4441 - 4450. [Abstract] [Full Text] [PDF] A. Tefferi and J. W. Vardiman Myelodysplastic Syndromes N. Engl. J. Med., November 5, 2009; 361(19): 1872 - 1885. [Full Text] [PDF] J. F. DiPersio, I. N. Micallef, P. J. Stiff, B. J. Bolwell, R. T. Maziarz, E. Jacobsen, A. Nademanee, J. McCarty, G. Bridger, and G. Calandra Phase III Prospective Randomized Double-Blind Placebo-Controlled Trial of Plerixafor Plus Granulocyte Colony-Stimulating Factor Compared With Placebo Plus Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients With Non-Hodgkin's Lymphoma J. Clin. Oncol., October 1, 2009; 27(28): 4767 - 4773. [Abstract] [Full Text] [PDF] S. W. Lane, D. T. Scadden, and D. G. Gilliland The leukemic stem cell niche: current concepts and therapeutic opportunities Blood, August 6, 2009; 114(6): 1150 - 1157. [Abstract] [Full Text] [PDF] M. Heuser, F. Kuchenbauer, B. Argiropoulos, S. Sekulovic, M. Leung, M. Stasiak, A. Ganser, and R. K. Humphries Priming reloaded? Blood, July 23, 2009; 114(4): 925 - 926. [Full Text] [PDF] A. K. Azab and I. M. Ghobrial Response: Sensitization initiated Blood, July 23, 2009; 114(4): 926 - 927. [Full Text] [PDF] C. N. Abboud Another nail in the AML coffin Blood, June 11, 2009; 113(24): 6045 - 6046. [Full Text] [PDF]

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