Analysis of the EphA2 Receptor Expression on Malignant PlasmaCells and Plasmacytoid Dendritic Cells in MGUS and MultipleMyeloma Patients

Identification of ligands for human gamma-delta T cells remains a major challenge. The EphA2 (Ephrin receptor A2) has been identified as a ligand for the Vdelta1 gammadelta TCR transductants. The EphA2 is often over-expressed in aggressive cancers mainly of epithelial origin; however, the expression in haematological malignancies has not been determined. Multiple myeloma (MM) is a malignancy of plasma cells located in bone marrow with a premalignant stage MGUS (monoclonal gammopathy of undetermined significance). Plasmacytoid dendritic cells (pDC) are known to promote the tumour plasma cell growth, survival and drug resistance in myeloma. The aim was to determine the expression of EphA2 on myeloma plasma cells (PC) and pDCs (CD123+, CD303+, CD304+) using multicolour flow cytometry in MGUS and newly diagnosed MM patients. We have used bone marrow (BM) and paired peripheral blood (PB) samples from MGUS (n=6) and MM patients (n=11). The age-matched healthy donors were used as controls (BM n=9, PB n=16). In MGUS and MM patients, we found prominent EphA2 expression on tumour plasma cells in BM, while plasmablasts were mostly negative. PDC have been identified uniformly EphA2+ in both PB and BM in healthy donors and in MGUS and MM patients. In summary, we showed the expression of EphA2 receptor on myeloma cells correlating with malignant transformation. Since EphA2-positivity has been confirmed on pDC in MGUS and MM patients, we hypothesize that large expansions of Vdelta1 gammadelta T cells are driven by the interactions with pDC and PC expressing the EphA2 in the tumour microenvironment.