IL-6 Down-Regulates CD33 Expression in Primary Myeloma Cells as Well as Myeloma Cell Lines.

Human primary myeloma cells show the marked heterogeneity of surface marker expression and morphology; possibly for myeloma cells lose the expression of PAX-5 and EBF, master genes of B cell lineage. As reported previously, we detected the expression of a myeloid marker, CD33, in the primary myeloma cells in about 10% out of 60 cases with overt myelomas as well as in 2 myeloma cell lines (Liu-01 and ILKM8 cells) by RT-PCR and flowcytometry using 4 different anti-CD33 antibodies. The expression of CD33 in these cells appeared to be well correlated to the monocytoid morphology with convoluted nuclei, and furthermore correlated to the increased expression of PU.1 and C/EBPα genes. Induction of CD33 expression was also found by the treatment with vitamin D3 in some primary myeloma cells as well as ILKM3 cell lines. This induction was not found in PAX-5(+) B cell lines (KUS and Raji cells). Interestingly, IL-6 down-regulated the expression of CD33 in Liu-01 and ILKM8 cell lines; if cultured with IL-6 (10 ng/ml) for 12 days, the expression of CD33 on Liu-01 cells completely disappeared. By IL-6 stimulation, the morphology of Liu-01 cells was also reversed to the morphology with round nuclei. Also, it is confirmed that IL-6 markedly suppressed the expression of PU.1 and C/EBPα genes in Liu-01 cells. Therefore, these data suggest that IL-6, a growth factor for myeloma cells, could reverse phenotypic conversion of non-B cell lineage such as CD33(+) myeloid/monocytoid cells to the B cell lineage.