CCR5 Chemokine Receptor Expression Can Promote Disease Progression in Non-Hodgkin’s Lymphoma.

Background: Non-Hodgkin’s lymphomas (nHL) represent heterogenous group of lymphoid malignancies derived from B and T lymphocytes, NK cells or histiocytes. Most of lymphomas are B-cell origin. Lymphoma cells can migrate to other organs and their migration could be linked to chemokines and their receptors. Chemokine receptors are expressed by many cell populations, including lymphoid cells, and their function is mediation of trafficking and localization particularly lymphocytes. CCR5 is predominantly expressed on Th1 cells, but also on dendritic cells, fibroblasts, endothelial and epithelial cells. Up-regulation of CCR5 expression is typical for nonneoplastic leukocytic infiltrates of nodal Hodgkin lymphoma. Its expression has been shown in hairy cell leukemia (HCL) and mantle cell lymphoma (MCL).

Aim: The purpose of this study was to determine CCR5 expression in lymph nodes derived from patients with nHL comparing to control reactive lymph nodes and if there was any correlation between CCR5 expression and proliferation marker Ki-67 and international prognostic index (IPI).

Material and methods: CCR5 gene expression was determined in 37 lymph nodes of lymphoma patients (26 B-cell lymphoma: 12 females and 14 males aged 26–73 years; 4 T-cell lymphoma: males aged 41–81 years; 7 Hodgkin’s lymphoma: 4 females and 3 males aged 21–58 years) and 25 reactive lymph nodes (15 females, 10 males, aged 18–59 years, median age 32 years). Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Scale of expression was 0–3 AU. Statistical analysis was performed using Kruskall-Wallis and Mann-Witney tests (p<0,05).

Results: Most of lymphoma lymph nodes (25/37) showed low CCR5 expression (0–1 AU). In reactive lymph nodes 18/25 had also low CCR5 expression. In B-cell lymphomas high CCR5 expression characterized HCL, Burkitt’s lymphoma and diffuse large B-cell lymphoma nodes. In pts with higher CCR5 expression there was positive correlation with Ki-67 proliferation marker (p=0,016; coefficient = 0,34) and IPI (p=0,047; coefficient = 0,298).

Conclusions: As there is a positive correlation between CCR5 expression and Ki-67 proliferation marker and IPI in non-Hodgkin’s lymphoma lymph nodes CCR5 may be associated with lymphoma progression.