Jakia Amin

Galectin-1 supports the survival of CD45RA(-) primary myeloma cells in vitro.

The survival and proliferation of human myeloma cells are considered to be heavily dependent on the microenvironment of bone marrow (BM). This study confirmed that galectin‐1 (Gal‐1) and SDF‐1α were produced by bone marrow mononuclear cells of myeloma patients. The addition of Gal‐1 and SDF‐1α to a serum‐free synthetic medium, maintained the viability of primary myeloma cells for 2 weeks similar to that before culture. While Gal‐1 reduced the viable cell number in CD45RA(+) B cell lines, it maintained the viability of CD45(−) U266 and CD45RA(−)RO(+) ILKM3 myeloma cell lines in the synthetic medium. This was confirmed with the transfection of the PTPRC (CD45) RA, ‐RB, or ‐RO gene into CD45(−) U266 cells. The combination of Gal‐1 and SDF‐1α significantly induced phosphorylation of Akt and IkB, while the phosphorylation of ERK1/2 was significantly reduced in CD45RA(+) U266 and Raji cells but not CD45(−) or CD45RA(−) U266 cells. Furthermore, we confirmed that Gal‐1 bound to CD45RA in CD45RA(+) Raji cells, and also physically interacted with β1‐integrin by immunoprecipitation followed by Western blotting and confocal microscopy. The results suggest that Gal‐1 has two different actions depending on its binding partner, and supports the survival of CD45RA(−) myeloma cells.

Induction of Multilineage Markers in Human Myeloma Cells and Their Down-Regulation by Interleukin 6

Human primary myeloma cells are well known to be heterogeneous with regard to morphology and surface phenotype. We confirmed the heterogeneous expression of such multilineage markers as CD33, CD7, CD56, CD4, and CD86 in primary myeloma cells from 20 patients with multiple myeloma and in 8 human myeloma cell lines. CD33 expression in the Liu01 cell line, a subclone of U266 cells, and in vitamin D3-treated ILKM3 cells, correlated with a monocytoid morphology featuring convoluted nuclei and with increased C/EBPα expression. CD56+ myeloma cells from some myeloma patients and the CD56+ (but not the CD56-) myeloma cell lines expressed neuronal cell markers, such as neuron-specific enolase and β-tubulin III. CD7 expression in Liu01 cells and forskolin-stimulated U266 cells coincided with the presence of large cytoplasmic granules, and these cells featured increased expression of perforin messenger RNA and significant natural killer cell activity. Interleukin 6 (IL-6), a growth factor for myeloma cells, down-regulated CD33, CD7, or CD56 expression in primary myeloma cells, as well as in Liu01 cells. Therefore, these data suggest that human myeloma cells are capable of inducing the expression of multilineage markers and that IL-6 can down-regulate such expression.

PPARβ-mediated growth suppression of baicalein and dexamethasone in human myeloma cells

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