Molecular and biological characterization of three novel interleukin-6-dependent human myeloma cell lines

Abstract

BACKGROUND AND OBJECTIVES: Established human myeloma cell lines (HMCL) have significantly contributed to the investigation of the biological aspects of multiple myeloma. Our study reports the molecular and biological characterization of three novel interleukin-6 (IL-6)-dependent HMCL (CMA-01, CMA-02, CMA-03) established from the malignant plasma cells of myeloma patients with extramedullary disease. DESIGN AND METHODS: The immunophenotype, cell growth characteristics, IL-6 pathway, chromosomal alterations and gene expression profiles of the three HMCL were investigated. RESULTS: The plasma cell origin of the three Epstein-Barr virus-negative HMCL was confirmed by immunophenotypic analysis. Cytogenetic and fluorescence in situ hybridization analyses revealed the presence of complex karyotypes with many numerical and structural chromosomal abnormalities. All three HMCL are positive for the t(8;14); CMA-01 and CMA-02 showed t(11;14) and t(14;16) translocations, respectively. The three HMCL grow slowly at a relatively low saturation density and depend on exogenous IL-6 for their survival and proliferation. The comparison of the gene expression profiles of the three HMCL versus those of the purified tumor plasma cells from which the cell lines were derived identified a set of differentially expressed genes mainly involved in the cell proliferation pathway. INTERPRETATION AND CONCLUSIONS: Extensively characterized large HMCL panels that reflect the heterogeneity of the disease may improve our understanding of the pathogenetic events and clinical progression of multiple myeloma.