Cell Cycle Analysis of Waldenström's Macroglobulinemia

Abstract Little is known about the DNA cell content and cell cycle characteristics of immunoglobulin (Ig) M monoclonal gammopathies. The autonomous clone appears to be rather heterogeneous, from mature B lymphocytes to plasma cells (PCs). We have evaluated the DNA cell content of 27 patients with IgM monoclonal gammopathies: 18 of them had Waldenstrom's macroglobulinemia (WM), and 9 were diagnosed with IgM-monoclonal gammopathy of undetermined significance (MGUS). To specifically analyze the cell cycle of the B lymphocyte and PC populations, we used a flow-cytometric double-staining technique with CD19/CD20/CD22 propidium iodide for B lymphocytes and CD38/CD138 propidium iodide for PCs. In 26 of 27 patients, both subsets of tumor cells (B lymphocyte and PC) showed a diploid DNA cell content (DNA index, 1). The median percentage of proliferating B lymphocytes, S-phase + G 2 /M-phase, was 1.8% (range, 0.4%-4.1%). This proliferative activity was significantly lower than that observed in nonmalignant cells (5.7%; range, 0.1%- 14.2%; P = 0.004) in the same sample. No differences were observed when comparing the proliferative activity of WM with that of IgM MGUS (median, 1.7% vs. 2.2%, respectively). Cell cycle characteristics of PCs were simultaneously evaluated in 9 patients, with 1.8% cells in S phase or G 2 /M phase. In summary, the cell cycle analysis showed that IgM monoclonal gammopathies are low-proliferative disorders, with a DNA ploidy pattern (diploid) clearly different from that of multiple myeloma.