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Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1.
Abstract
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.
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“which regulate trafficking of human CLL cells between PB, lymphoid organs, and BM”
From RhoH is critical for cell-microenvironment interactions in chronic lymphocytic leukemia in mice and humans (2012) · cites this paper as [6]
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“These NLCs express and produce chemokines, such as CXCL12 and CXCL13”
From RhoH is critical for cell-microenvironment interactions in chronic lymphocytic leukemia in mice and humans (2012) · cites this paper as [6]
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“and thus promote interaction with the microenvironment necessary for their survival and proliferation.6,7”
From RhoH is critical for cell-microenvironment interactions in chronic lymphocytic leukemia in mice and humans (2012) · cites this paper as [6]
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Metadata
- Authors
- Burger, J. A., Tsukada, N., Burger, M., Zvaifler, N. J., Dell'Aquila, M., & Kipps, T. J.
- Affiliations
- 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.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2000-10-15
- Volume
- 96
- Issue
- 8
- Pages
- 2655-2663
- ISSN
- 1528-0020
- 0006-4971
- Cited by
- 607
- References
- 2
- Language
- en
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