Differential expression of chemokine receptors in B cell malignancies

Chemokines are a family of 8-10 kDa proteins with a wide range of biologica l activities including the regulation of leukocyte trafficking, modulation of haemopoietic cell proliferation and adhesion to extracellular matrix mol ecules. 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 ce ll chronic lymphocytic leukaemia (B-CLL; 31 cases), multiple myeloma (10 ca ses), mantle cell lymphoma (MCL, four cases), follicular lymphoma (FL, thre e cases) and hairy cell leukaemia (HCL, five cases). We demonstrate that CX CR4, CXCR5 and CCR6 are differentially expressed in these B lymphoprolifera tive disorders depending on the maturational stage of the malignant B cell population investigated. In particular, we found that CXCR4 is strongly exp ressed on immature ALL blasts whereas no surface immunoreactivity for CXCR5 , CCR5 and CCR6 was observed. By contrast, non-Hodgkin's lymphomas (NHLs) c orresponding to more mature peripheral B cell subsets (ie B-CLL and MCL) ex hibited high expression levels of CXCR4 and CXCR5, Analysis of terminally d ifferentiated 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 case s of HCL, representing the first example of cross-lineage aberrant chemokin e receptor expression in malignant haemopoietic cells.