Differential expression of chemokine receptors in B cell malignancies

Abstract

Chemokines are a family of 8-10 kDa proteins with a wide range of biological activities including the regulation of leukocyte trafficking, modulation of haemopoietic cell proliferation and adhesion to extracellular matrix molecules. Using a panel of chemokine receptor-specific monoclonal antibodies (MoAb) in a multicolour flow cytometry approach we analysed the expression of the lymphocyte-associated chemokine receptors CXCR4, CXCR5, CCR5 and CCR6 in B cell acute lymphoblastic leukaemia (precursor B-ALL; six cases), B cell chronic lymphocytic leukaemia (B-CLL; 31 cases), multiple myeloma (10 cases), mantle cell lymphoma (MCL, four cases), follicular lymphoma (FL, three cases) and hairy cell leukaemia (HCL, five cases). We demonstrate that CXCR4, CXCR5 and CCR6 are differentially expressed in these B lymphoproliferative disorders depending on the maturational stage of the malignant B cell population investigated. In particular, we found that CXCR4 is strongly expressed on immature ALL blasts whereas no surface immunoreactivity for CXCR5, CCR5 and CCR6 was observed. By contrast, non-Hodgkin's lymphomas (NHLs) corresponding to more mature peripheral B cell subsets (ie B-CLL and MCL) exhibited high expression levels of CXCR4 and CXCR5. Analysis of terminally differentiated myeloma cells revealed a down-regulation of CXCR4, CXCR5 and CCR6. CCR5, which is not expressed in normal B cells, was also absent from the majority of NHLs. However, CCR5 staining was seen in three of five cases of HCL, representing the first example of cross-lineage aberrant chemokine receptor expression in malignant haemopoietic cells. Leukemia (2001) 15, 752-756.

Expression and function of chemokine receptors in human multiple myeloma

“…In line with our results on the expression of CXCR4 on primary MM cells and MM cell lines is a recent study by Dü rig et al, 23 where they described that primary MM cells do express CXCR4. However, in that study they did not investigate the migratory response of the cells to SDF-1.…”

“…8 In contrast to a number of B cell tumors, including chronic lymphocytic leukemia (CLL), 23,24 we could not detect any expression of CXCR5 mRNA or protein in MM cells. The difference in CXCR5 expression on B-CLL and MM cells is likely due to the fact that these cells represent different stages of differentiation within the B cell lineage.…”

“…7,[20][21][22] Human MM cells have been demonstrated to express CXCR4, but the functionality of these receptors has not been investigated previously. 23 Here, we systematically investigated the expression of chemokine receptors in MM cell lines. The functionality of receptors was tested by agonist-induced calcium mobilization and cell migration.…”

Molecular pathology of primary intraocular lymphoma

“…149 High expression of CXCR4 has also been shown in mantle cell lymphoma and B-cell acute lymphoblastic and chronic lymphocytic leukemia cells. 150 The present study shows strong expression of CXCR5 and CXCR4 on PIOL cells and of BLC on RPE cells. The findings of BLC that functions as a homing chemokine expressed in RPE and CXCR5 that is detected in PIOL cells may be one important mechanism for tumor cell homing and localizing between the RPE and Bruch's membrane in the eye.…”

PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells

“…In addition, it has been demonstrated that corresponding receptors of these cytokines are expressed by MM cells and therefore these cytokines can play a role in MM. [17][18][19][20][21][22][23][24][25][26][27][28] Nevertheless, with exception of IL-6, the precise role of these cytokines in MM is still unclear.…”