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AUTHORS: M.M. Kawano, K.-I. Otsuyama, S. Liu
Laboratory of Cellular Signal Analysis, Graduate School of Medicine, Yamaguchi University, Ube, Japan
By Lynne Lederman, PhD
Primary cells from patients with multiple myeloma and myeloma cell lines show lineage plasticity, phenotypic heterogeneity, and genetic instability. Phenotypic heterogeneity and plasticity is indicated by the presence of multi-lineage cell surface markers in cells that have lost expression of the master B cell lineage gene Pax-5. CD33 is expressed on Liu01, a subclone of U266 cells. This subclone and other lines may express CD56, neuron-specific enolase (NSE), and other neuronal cell markers after differentiation into neuronal-like cells. CD56 + myeloma cells also express CD7 with NK (natural killer) activity. IL-6 downregulates the expression of both CD33 and CD56 in myeloma cells and is associated with a change in morphology. Dr. Kawano hypothesized that the loss of Pax-5 at the stage of B cell lineage differentiation where germinal center B cells would normally move into the immature plasma cell stage may result in what he calls “stone cells” or stem cell-like cells dropping out of the lineage. These stone cells are stem-cell like in their ability to differentiate into multilineage cells types, including myeloid, NK, and neuronal cells, and under the influence of IL-6 are capable of proliferation and self-renewal. Whether the expression of CD56, CD33, or other cell surface markers has prognostic value remains to be determined.