Cycloxygenase-2 (COX-2) Expression Is More in Clonal Plasma Cells.

Multiple myeloma is characterised by deregulated cytokine network with secretion of inflammatory cytokines. Recent studies have showed the independent poor prognostic value of COX-2 expression in myeloma. We have here studied the COX-2 expression in plasma cells from patients with myeloma, monoclonal gammopathy of undetermined significance (MGUS), Waldenstrom’s Macroglobulinemia (WM) and compared with the COX-2 expression by normal plasma cells. Methods: Our study included bone marrow samples from 34 patients (Lymphoma: 15; myeloma: 10; MGUS: 7; WM: 1; Amyloidosis: 1). Mononuclear cells were harvested from the bone marrow samples by density gradient sedimentation using Lymphoprep TM from Axis-Shield, Norway. Mononuclear cells were stained with PE conjugated CD 38 (BD Bioscience) and APC conjugated CD138 (BD Bioscience). FITC conjugated IgG against human COX-2 (Cayman Chemical) was used to study the expression of cycloxygenase-2 following permeabilization with fix and perm kit (Caltag). Flow cytometry was performed on a Becton Dickinson FACS vantage with appropriate isotype controls. The colorectal cell line HT- 29 and human myeloma cell line RPMI 8226 were used as positive controls and the flow results are validated by western blotting and Prostaglandin E2 EIA assay (Cayman Chemical). Results: HT-29 cell line showed a peak fluorescence of 58 for COX-2, where as RPMI 8226 cell line revealed peak fluorescence of 141. Median plasma cell count in bone marrow of patients with MGUS was 2 %( range 2–6%). Plasma cells from MGUS patients revealed median peak fluorescence for COX-2 was 37(range: 9–74). Median plasma cell count in bone marrow of patients with myeloma was 25% (range: 10–59%). Median peak fluorescence for COX-2 in plasma cells from patients with myeloma was 24(range: 10–85). Median plasma cell count in bone marrow of patients with lymphoma was 1 %( range1–4%). Median peak fluorescence for COX-2 in plasma cells from patients with lymphoma was 11(range: 2–38). Conclusions: Our study reveals COX-2 expression is more in clonal plasma cells as compared to normal plasma cells. Studies are needed to ascertain the role of COX-2 in oncogenesis in myeloma and to discover how COX-2 expression leads to poor outcome in patients with myeloma. This information may lead to the therapeutic role of selective COX-2 inhibitors in the therapy of myeloma.