Distinct IL-6 signal transduction leads to growth arrest and death in B cells or growth promotion and cell survival in myeloma cells

WC Cheung, B Van Ness - Leukemia, 2002 - nature.com
WC Cheung, B Van Ness
Leukemia, 2002nature.com
In B cell development, interleukin-6 (IL-6) induces terminal maturation of B lymphocytes into
antibody producing plasma cells. Terminal differentiated B cells cell cycle arrest and death
follows. In contrast, IL-6 acts as a growth factor for malignant myeloma plasma cells and in
some cases protects them from therapeutic treatment. In this study, we examined two cell
lines that show different responses to IL-6. Lymphoblastoid CESS cells respond to IL-6 by
terminally differentiating into antibody producing plasma cells, cell cycle arrest, and undergo …
Abstract
In B cell development, interleukin-6 (IL-6) induces terminal maturation of B lymphocytes into antibody producing plasma cells. Terminal differentiated B cells cell cycle arrest and death follows. In contrast, IL-6 acts as a growth factor for malignant myeloma plasma cells and in some cases protects them from therapeutic treatment. In this study, we examined two cell lines that show different responses to IL-6. Lymphoblastoid CESS cells respond to IL-6 by terminally differentiating into antibody producing plasma cells, cell cycle arrest, and undergo cell death. Continuous addition of IL-6 to these cells induces transient activation of STAT3, SHP-2 phosphorylation, and does not alter bcl-X L and c-myc expression. In contrast, the myeloma line ANBL6 proliferates when stimulated with IL-6 and this correlates with prolonged STAT3 activation and up-regulation of bcl-X L and c-myc. Interestingly, gp130-associated SHP-2 phosphorylation was detected in the IL-6-induced CESS cells but not myeloma cell lines. The data show a very distinct IL-6 signal transduction and kinetics in these cell lines and the distinct molecular events correlate closely to the cell fate of the lymphoblast and myeloma cell lines.
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