Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell–derived factor-1
Top Cited Papers
Open Access
- 15 October 2000
- journal article
- Published by American Society of Hematology in Blood
- Vol. 96 (8), 2655-2663
- https://doi.org/10.1182/blood.v96.8.2655
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.Keywords
This publication has 59 references indexed in Scilit:
- Stromal Cell-derived Factor-1α Associates with Heparan Sulfates through the First β-Strand of the ChemokineJournal of Biological Chemistry, 1999
- The α-Chemokine, Stromal Cell-derived Factor-1α, Binds to the Transmembrane G-protein-coupled CXCR-4 Receptor and Activates Multiple Signal Transduction PathwaysJournal of Biological Chemistry, 1998
- Associations between TGF-β1 receptors in human bone marrow stromal cellsBritish Journal of Haematology, 1998
- Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar developmentNature, 1998
- The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tractNature, 1998
- Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1Nature, 1996
- Apoptosis and Macrophage‐Mediated Cell Deletion in the Regulation of B Lymphopoiesis in Mouse Bone MarrowImmunological Reviews, 1994
- Regulation of Hemopoiesis by Bone Marrow Stromal Cells and Their ProductsAnnual Review of Immunology, 1990
- Symbiotic culture of mouse leukaemias: Regulation of cell interaction by an activity of serumVirchows Archiv B Cell Pathology Including Molecular Pathology, 1980
- Thymic nurse cells. Lymphoepithelial cell complexes in murine thymuses: morphological and serological characterizationThe Journal of Experimental Medicine, 1980