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Mechanisms of regulation of CXCR 4/SDF-1 (CXCL 12)– dependent migration and homing in multiple Mechanisms of regulation of CXCR 4/SDF-1 (CXCL 12)– dependent migration and homing in multiple myeloma by Yazan Alsayed, Hai Ngo, Judith Runnels, Xavier Leleu, Ujjal K. Singha, Costas M. Pitsillides, Joel A. Spencer, Teresa Kimlinger, Joanna M. Ghobrial, Xiaoying Jia, Ganwei Lu, Michael Timm, Ashok Kumar, Daniel Côté, Israel Veilleux, Karen E. Hedin, G. David Roodman, Thomas E. Witzig, Andrew L. Kung, Teru Hideshima, Kenneth C. Anderson, Charles P. Lin, and Irene M. Ghobrial Blood Volume 109(7): 2708 -2717 April 1, 2007 © 2007 by American Society of Hematology

CXCR 4 and SDF 1 expression in patients with MM. (A) Surface expression of CXCR 4 and SDF 1 expression in patients with MM. (A) Surface expression of CXCR 4 on plasma cells in the peripheral blood (PB) and bone marrow (BM) of patients with MM. Median percentage expression of CXCR 4 in plasma cells in the PB was 60% (range, 9%-96%) com. . . Yazan Alsayed et al. Blood 2007; 109: 2708 -2717 © 2007 by American Society of Hematology

YFP-CXCR 4 localization in response to SDF-1. Yazan Alsayed et al. Blood 2007; 109: YFP-CXCR 4 localization in response to SDF-1. Yazan Alsayed et al. Blood 2007; 109: 2708 -2717 © 2007 by American Society of Hematology

Migration and motility in response to SDF-1. Yazan Alsayed et al. Blood 2007; 109: Migration and motility in response to SDF-1. Yazan Alsayed et al. Blood 2007; 109: 2708 -2717 © 2007 by American Society of Hematology

Regulation of migration by inhibitors of the CXCR 4 signaling pathway. Yazan Alsayed et Regulation of migration by inhibitors of the CXCR 4 signaling pathway. Yazan Alsayed et al. Blood 2007; 109: 2708 -2717 © 2007 by American Society of Hematology

Signaling pathways regulated by SDF 1/CXCR 4 in MM. (A) Immunoblotting for p. ERK Signaling pathways regulated by SDF 1/CXCR 4 in MM. (A) Immunoblotting for p. ERK and p. AKT, demonstrating rapid activation in response to SDF-1 30 n. M in a time-dependent fashion at 1, 3, and 5 minutes. Yazan Alsayed et al. Blood 2007; 109: 2708 -2717 © 2007 by American Society of Hematology

In vivo flow cytometry and confocal microscopy imaging of MM. 1 S in the In vivo flow cytometry and confocal microscopy imaging of MM. 1 S in the presence or absence of AMD 3100. Yazan Alsayed et al. Blood 2007; 109: 2708 -2717 © 2007 by American Society of Hematology

Bioluminescence imaging of Luc+ MM. 1 S cells injected intravenously into the tail veins Bioluminescence imaging of Luc+ MM. 1 S cells injected intravenously into the tail veins of SCID/NOD mice. Yazan Alsayed et al. Blood 2007; 109: 2708 -2717 © 2007 by American Society of Hematology