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Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3658-3667
Chronic Lymphocytic Leukemia B Cells Express Functional
CXCR4 Chemokine Receptors That Mediate Spontaneous Migration
Beneath Bone Marrow Stromal Cells
Jan A. Burger,
Meike Burger, and
Thomas J. Kipps
From the Department of Medicine, the Division of Hematology/Oncology,
University of California, San Diego, La Jolla, CA; and the Department
of Immunology, The Scripps Research Institute, La Jolla, CA.
Chemokines play a central role for lymphocyte trafficking and
homing. The mechanisms that direct the tissue localization of B cells
from patients with chronic lymphocytic leukemia (B-CLL) are unknown. We
found that CLL B cells express functional CXCR4 receptors for the
chemokine stromal cell-derived factor-1 (SDF-1), as demonstrated by
receptor endocytosis, calcium mobilization, and actin polymerization
assays. Moreover, CLL B cells displayed chemotaxis to this chemokine
that could be inhibited by monoclonal antibodies (MoAbs) against CXCR4,
pertussis toxin, or Wortmannin, a phosphatidylinositol 3-kinase
inhibitor. That this chemotaxis may be involved in the homing of CLL
cells is argued by studies in which CLL B cells were cocultured with a
murine marrow stromal cell line that secretes SDF-1. Within 2 hours,
CLL B cells spontaneously migrated beneath such stromal cells in vitro
(pseudoemperipolesis). This migration could be inhibited by
pretreatment of CLL B cells with anti-CXCR4 MoAbs, SDF-1 , or
pertussis-toxin. Furthermore, we noted strong downmodulation of CXCR4
on CLL B cells that migrated into the stromal cell layer. These
findings demonstrate that the chemokine receptor CXCR4 on CLL B cells
plays a critical role for heterotypic adherence to marrow stromal cells
and provide a new mechanism to account for the marrow infiltration by
neoplastic B cells.
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[Abstract]
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J. A. Burger, N. Tsukada, M. Burger, N. J. Zvaifler, M. Dell'Aquila, and T. J. Kipps
Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1
Blood,
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[Abstract]
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R. D. M. Soede, Y. M. Wijnands, M. Kamp, M. A. van der Valk, and E. Roos
Gi and Gq/11 proteins are involved in dissemination of myeloid leukemia cells to the liver and spleen, whereas bone marrow colonization involves Gq/11 but not Gi
Blood,
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[Abstract]
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