Analysis of natural killer‐associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications

Abstract
The aim of this study was to analyse the expression of NK‐associated antigens in both peripheral blood and bone marrow lymphocytes from a large series of newly diagnosed multiple myeloma patients. 112 patients with untreated multiple myeloma (MM) were included in the study. 36 sex‐ and age‐matched healthy volunteers were used as controls for peripheral blood (PB) studies and 14 for the bone marrow (BM) studies. Simultaneous stainings with the CD3/CD56, CD2/CD16 and CD8/CD57 monoclonal antibodies were systematically performed in PB and CD3/CD56 and CD2/CD16 in BM in order to analyse their relationship with the clinical and biological characteristics of the disease and survival. The expression of NK‐associated antigens (CD56, CD16 and CD57) assessed within the lymphoid gate, was significantly increased (P < 0.001) in the PB of MM patients both in relative and absolute numbers. In the BM a significant increase in the percentage of CD56+ lymphocytes (P < 0.001) was also observed; in contrast, the proportion of CD16+ cells did not differ significantly from that of normal BM samples. The number of CD56+CD3 lymphocytes increased significantly within high‐risk patients (869 ± 671) as compared to intermediate (388 ± 212) and low‐risk patients (274 ± 199) (P = 0.04). Moreover, patients with high values of CD56+CD3 lymphocytes showed a statistically significant association with several adverse prognostic factors including anaemia, hypoalbuminaemia, renal failure, high β2M, DNA diploidy and high S‐phase plasma cells. In addition, patients with higher absolute numbers of PB CD56+CD3 lymphocytes displayed a poorer prognosis, whereas patients with higher values of CD57+CD8 cells had a better outcome.