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Blood, 15 October 2000, Vol. 96, No. 8, pp. 2655-2663

PLENARY PAPER

Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1

Jan A. Burger, Nobuhiro Tsukada, Meike Burger, Nathan J. Zvaifler, Marie Dell'Aquila, and Thomas J. Kipps

From the Department of Medicine, Division of Hematology/Oncology, and the Division of Rheumatology, Allergy, and Immunology, University of California at San Diego; and the Department of Immunology, The Scripps Research Institute, La Jolla, CA.

A subset of blood cells from patients with B-cell chronic lymphocytic leukemia (CLL) spontaneously differentiates in vitro into large, round, or fibroblast-like adherent cells that display stromal cell markers, namely vimentin and STRO-1. These cells also express stromal cell-derived factor-1 (SDF-1), a CXC chemokine that ordinarily is secreted by marrow stromal cells. Leukemia B cells attach to these blood-derived adherent cells, down-modulate their receptors for SDF-1 (CXCR4), and are protected from undergoing spontaneous apoptosis in vitro. Neutralizing antibodies to SDF-1 inhibit this effect. Moreover, the rapid deterioration in the survival of CLL B cells, when separated from such cells, is mitigated by exogenous SDF-1. This chemokine also results in the rapid down-modulation of CXCR4 and activation of p44/42 mitogen-activated protein-kinase (ERK 1/2) by CLL B cells in vitro. It is concluded that the blood of patients with CLL contains cells that can differentiate into adherent nurse-like cells that protect leukemia cells from undergoing spontaneous apoptosis through an SDF-1-dependent mechanism. In addition to its recently recognized role in CLL B-cell migration, SDF-1-mediated CLL B-cell activation has to be considered a new mechanism involved in the microenvironmental regulation of CLL B-cell survival.

© 2000 by The American Society of Hematology.
 

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J. Kijowski, M. Baj-Krzyworzeka, M. Majka, R. Reca, L. A. Marquez, M. Christofidou-Solomidou, A. Janowska-Wieczorek, and M. Z. Ratajczak
The SDF-1-CXCR4 Axis Stimulates VEGF Secretion and Activates Integrins but does not Affect Proliferation and Survival in Lymphohematopoietic Cells
Stem Cells, September 1, 2001; 19(5): 453 - 466.
[Abstract] [Full Text] [PDF]



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