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Blood, 15 July 2004, Vol. 104, No. 2, pp. 502-508.
Prepublished online as a Blood First Edition Paper on March 4, 2004; DOI 10.1182/blood-2003-09-3103.
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NEOPLASIA
Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas
Livio Trentin,
Anna Cabrelle,
Monica Facco,
Davide Carollo,
Marta Miorin,
Alicia Tosoni,
Paola Pizzo,
Gianni Binotto,
Linda Nicolardi,
Renato Zambello,
Fausto Adami,
Carlo Agostini, and
Gianpietro Semenzato
From the Department of Clinical and Experimental Medicine, Clinical Immunology Branch, Padua University School of Medicine, Venetian Institute for Molecular Medicine (VIMM), Centro di Eccellenza per la Ricerca Biomedica, Padova, Italy; and Department of Experimental Biomedical Sciences, University of Padova, Padova, Italy.
This study investigated the role of several chemokines and their receptors on malignant B lymphocytes recovered from 13 patients with chronic lymphocytic leukemia (CLL), 9 with hairy cell leukemia (HCL), 5 with mantle cell lymphoma (MCL), 5 with marginal zone B-cell lymphoma (MZL), 6 with small lymphocytic lymphoma (SLL), and 5 with follicular cell lymphoma (FCL). Flow cytometry analysis demonstrated that CXCR4 and CXCR5 were expressed on all malignant and normal B cells. Considering CC receptors, CCR1 was expressed in 70% of patients with CLL and 40% of those with HCL but was lacking in patients with MCL, MZL, SLL, and normal B cells. CCR2 showed a heterogeneous pattern of expression. CCR3 was found in almost all patients with CLL and in the majority of those with HCL, whereas it was usually lacking in patients with MZL and SLL and in healthy subjects. CCR5 was expressed in patients with HCL and MCL. Migration assays showed that different chemokines, mainly CXCL12 and CXCL13, are able to trigger migration of malignant B lymphocytes. Some of these chemokines induce calcium mobilization. These data indicate that different patterns of chemokine receptor expression identify different malignant B-cell subsets and that these receptors are functional and might play a role in malignant B-cell circulation. (Blood. 2004;104:502-508)
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