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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.
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