Despite typical features described for marginal zone lymphoma (MZL), the distinction of MZL from other small mature B-cell leukemias/lymphomas (in particular atypical chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) or lymphoplasmacytic lymphoma (LPL) may be still difficult due to the lack of immunological positive markers of MZL and before complementary analysis (histology, karyotype). In order to find new markers, we conducted proteomic analyses on plasma membrane microparticles derived from malignant cells and identified the Toll-like receptor homolog CD180 protein as a candidate marker of MZL. This protein, also called RP105, is a leucin-rich repeat type 1 membrane protein with high extra-cellular homology to the LPS receptor. The relevance of this marker was evaluated in peripheral blood B-cells from 25 normal controls and 91 patients (MZL, n=30; CLL, n=30; MCL, n=16 and LPL, n=15) by flow cytometry.
As already described by Porakishvili et al, normal B-cells displayed higher CD180 expression than CLL B-cells (MFI=5940+/− 1708 and MFI=150 +/− 794.4, respectively p<0.001, Mann-Whitney test). We observed also a low CD180 expression in MCL (1292 +/− 1084, p<0.001) and LPL (1443+/− 905.5, p<0.001), not different from CLL and significantly lower than control B-cells (see figure). On the contrary, staining of MZL was not different from controls (7856 +/− 1030, p>0.05), but significantly higher than CLL, MCL and LPL. In addition, among the lymphomas derived from MZ B-cell, CD180 expression was statistically higher in splenic diffuse red pulp lymphoma (SDRPL) than MZL. Intra-cellular staining of CD180 showed a significant positivity in tumoral B-cell tested (CLL, MCL, MZL), suggesting that the protein is produced but its expression at the cell surface is impaired. The reasons of this alteration are not known. Furthermore, cross-linking of this receptor induced a stronger increase of CD86 expression at the cell surface in MZL than in control B-cells and in CLL B-cells, suggesting an activated NF-kB pathway.
These results strongly suggest that CD180 may be the first positive immunological marker for MZL, able to distinguish MZL from CLL, MCL, LPL in blood samples. Large prospective studies are needed to precise its diagnosis impact and its expression in the different subtypes of MZL.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.