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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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K. Balabanian, A. Foussat, L. Bouchet-Delbos, J. Couderc, R. Krzysiek, A. Amara, F. Baleux, A. Portier, P. Galanaud, and D. Emilie
Interleukin-10 modulates the sensitivity of peritoneal B lymphocytes to chemokines with opposite effects on stromal cell-derived factor-1 and B-lymphocyte chemoattractant
Blood,
January 15, 2002;
99(2):
427 - 436.
[Abstract]
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C. Hernandez-Lopez, A. Varas, R. Sacedon, E. Jimenez, J. J. Munoz, A. G. Zapata, and A. Vicente
Stromal cell-derived factor 1/CXCR4 signaling is critical for early human T-cell development
Blood,
January 15, 2002;
99(2):
546 - 554.
[Abstract]
[Full Text]
[PDF]
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N. E. Kay, T. J. Hamblin, D. F. Jelinek, G. W. Dewald, J. C. Byrd, S. Farag, M. Lucas, and T. Lin
Chronic Lymphocytic Leukemia
Hematology,
January 1, 2002;
2002(1):
193 - 213.
[Abstract]
[Full Text]
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A. Bernal, R. D. Pastore, Z. Asgary, S. A. Keller, E. Cesarman, H.-C. Liou, and E. J. Schattner
Survival of leukemic B cells promoted by engagement of the antigen receptor
Blood,
November 15, 2001;
98(10):
3050 - 3057.
[Abstract]
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J. L. Gabrilove
Hematologic Malignancies: An Opportunity for Targeted Drug Therapy
Oncologist,
October 1, 2001;
6(2008):
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J. L. Gabrilove
Angiogenic Growth Factors: Autocrine and Paracrine Regulation of Survival in Hematologic Malignancies
Oncologist,
October 1, 2001;
6(2008):
4 - 7.
[Abstract]
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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,
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[Abstract]
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