Cell cycle analysis of Waldenstrom's macroglobulinemia

Area of Science:

• Hematology
• Oncology
• Cell Biology

Background:

• Immunoglobulin (Ig) M monoclonal gammopathies, such as Waldenstrom's macroglobulinemia (WM) and IgM monoclonal gammopathy of undetermined significance (MGUS), comprise a heterogeneous clone from B lymphocytes to plasma cells (PCs).
• Limited data exists on the DNA cell content and cell cycle kinetics of these disorders.

Purpose of the Study:

• To evaluate the DNA cell content and cell cycle characteristics of B lymphocytes and plasma cells in patients with IgM monoclonal gammopathies.
• To differentiate the cell cycle profile of IgM monoclonal gammopathies from other plasma cell disorders like multiple myeloma.

Main Methods:

• Flow-cytometric analysis using a double-staining technique with specific cell surface markers (CD19/CD20/CD22 for B lymphocytes, CD38/CD138 for PCs) and propidium iodide for DNA content and cell cycle assessment.
• Evaluation of 27 patients with IgM monoclonal gammopathies (18 WM, 9 MGUS).

Main Results:

• A diploid DNA cell content (DNA index = 1) was observed in 26 of 27 patients for both B lymphocyte and PC subsets.
• The median percentage of proliferating B lymphocytes (S-phase + G2/M-phase) was 1.8%, significantly lower than nonmalignant cells (5.7%; P = 0.004).
• No significant difference in proliferation was found between WM and IgM MGUS. Plasma cells also showed low proliferation (1.8% in S or G2/M phase).

Conclusions:

• IgM monoclonal gammopathies are characterized by low proliferative activity and a diploid DNA pattern.
• These cell cycle features differentiate IgM monoclonal gammopathies from the typically aneuploid and more proliferative multiple myeloma.