Xue-Guang Zhang

Interleukin-6 dependence of advanced malignant plasma cell dyscrasias.

The authors, and others, clearly have established that interleukin‐6 (IL‐6) is the major growth factor for human myeloma cells in vitro. It is a critical conceptual point whether or not IL‐6 remains involved in the final phases of disease progression in malignant plasma cell dyscrasias. To answer this question, the authors evaluated the in vitro IL‐6 dependence of the proliferation of myeloma cells from the bone marrow of 13 patients with advanced multiple myeloma (MM) and from the peripheral blood of 13 patients with plasma cell leukemia (seven primary and six secondary cases). Their results show that myeloma cell growth was totally dependent on IL‐6 in 25 of 26 patients. Myeloma cells of only one patient did not respond to IL‐6 in vitro. Actually, the cells from this patient were not proliferating in vivo. Identical patterns of IL‐6 dependence of myeloma cells were found in the peripheral blood and bone marrow from four patients with PCL. The authors conclude that, in the terminal phase of malignant plasma cell dyscrasias, tumoral growth is totally dependent on IL‐6 in vitro. This observation is critical in considering the investigation of anti‐IL‐6 therapy in patients with advanced MM. Cancer 1992; 69:1373‐1376.

Interleukin-6 is a Major Myeloma Cell Growth Factor In Vitro and In Vivo Especially in Patients with Terminal Disease

Multiple myeloma (MM) is a B cell malignancy characterized by the slow proliferation, primarily in the bone marrow, of a clone of malignant plasma cells that destroy the bone tissue. This disease is lethal in any case and little therapeutic progress has been achieved these last 20 years. Although myeloma cells poorly proliferate in vivo, the in vivo labelling index of the myeloma cells (LI = percentage of myeloma cells in the S-phase) constitutes one of the best prognostic factors (Durie 1980). This emphasizes clearly the importance of knowing the cytokines that control tumoral growth for further improving the therapeutic control of this disease.

Delay and not deficiency in cap formation of peripheral blood B cells in patients with multiple myeloma

A major problem in the study of peripheral blood (PB) B cells from patients with multiple myeloma (MM) is the distinction between the cells really able to synthesize membrane (m) immunoglobulins (Ig) and those able only to absorb serum Ig passively, since the lymphocytes of such patients are bathed in very high concentrations of monoclonal Ig. In order to reappraise PB B cells (including putative pre-B cells) in MM, we have used three different criteria: (a) the capacity of PB B cells to cap mIg when triggered by an anti-Ig; (b) the presence of B-cell differentiation antigens (CD19, CD20, CD21, and CD37) as specific B-cell markers; and (c) the expression of cytoplasmic μ heavy chain as a marker of pre-B cells. We have found that, in active myeloma (N=13), the percentages and absolute numbers of PB B cells able to cap mIg (4.25%; 45.43 cells/mm3) were significantly lower than those in healthy donors (8.4%; 151.2 cells/mm3) and those in stable MM (7.67%; 134.39 cells/mm3). In addition, the capping formation in patients with stable or active MM was significantly delayed compared to that in healthy donors. For all the normal individuals and patients investigated, there has been found an excellent correlation between the percentages and absolute numbers of PB B cells able to cap their mIg and those of PB mononuclear cells bearing the four B cell-specific differentiation antigens: CD19, CD20, CD21, and CD37. Finally, virtually no pre-B cells bearing cytoplasmic μ chains have been identified in the peripheral blood from healthy donors and patients with MM.