Abstract | There is strong evidence implicating microenvironmental sensors, including toll-like receptors (TLRs), in the pathobiology of chronic lymphocytic leukaemia (CLL).1, 2 We have previously demonstrated that the orphan TLR CD180 is heterogeneously expressed on peripheral blood (PB) CLL cells in ~60% of cases.3 Ligation of CD180 with monoclonal antibody (mAb) resulted in the activation, cycling and proliferation of PB CLL cells.4 We further demonstrated that CD180 engagement utilised two, often alternative signalling pathways mediated by protein kinase B (AKT) or p38 mitogen-activated protein kinase (p38MAPK), which corresponded with CLL cell survival and apoptosis, respectively. Moreover, in our hands, ligation of CD180 rewired immunoglobulin M (IgM)-mediated signalling from AKT to p38MAPK pathway.5 Given the important role of proliferation centres in the pathobiology of CLL,6 we investigated for the first time the expression of CD180 in the lymph nodes (LNs) of 55 untreated and 55 treated patients with CLL and six normal controls, using immunohistochemistry and calculation of a semi-quantitative H-score.7 The paraffin sections of the LNs were collected between 1992 and 2013, and the patients were treated with various regimens applicable to the collection period. |
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