Circulating Ki67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy

Abstract

Aims-To estimate the proportion and nature of the proliferating (Ki67+) circulating lymphocytes in a series ofpatients with multiple myeloma and monoclonal gammopathy of unknown significance (MGUS) and to correlate this with other clinical and laboratory parameters, using blood from healthy adults as a control. To investigate the extent to which the B and T lymphoid components are involved in progression and/or control of disease. Methods-Blood lymphocytes from 15 patients with multiple myeloma, 10 patients with MGUS and 10 healthy adults were analysed using a sequential double immunoenzymatic staining technique. Antibodies directed against Ki67 were used to detect cells in cycle, CD3, CD4, and CD8 to identify T cells, HLA-Dr as a marker for B cells and activated T cells, and CDllb as a marker for natural killer cells. Polyclonal antibodies directed against the K and k immunoglobulin light chains were also used to detect B cells. Results-The proportion of proliferating (Ki67 +) lymphocytes was significantly higher in patients with multiple myeloma (6-8 ± 2 6) and MGUS (3-5 ± 1.1) compared with the normal controls (1.69±0.3); this was also true when multiple myeloma and MGUS cases were compared. In multiple myeloma and MGUS over 50% of the Ki67 + cells were activated T lymphocytes (CD3+/HLA-Dr+); a minority (11%) were non-clonal B lymphocytes. In contrast to controls (6-7 ± 1 9), in patients with multiple myeloma and MGUS the proportion of proliferating T cells expressing CD8 (23.6+12.5 and 15-3+7 7, respectively) and CD11b (13+8-7 and 11-6±3-9, respectively) was higher. In multiple myeloma there was a positive correlation between the proportion of Ki67 + lymphocytes, β-2-microglobulin concentrations and disease stage. Conclusions-Although the number of patients investigated is small, this study suggests that Ki67 expression in blood lymphocytes from patients with multiple myeloma may be a good prognostic indicator for aggressive disease and may help to distinguish multiple myeloma from MGUS. The activated proliferating T cells in these diseases may represent an immunological reaction against the tumour.