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


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.


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.
Verdelli
Donata
D
U.O. Ematologia 2, Ospedale Maggiore IRCCS, Milan, Italy.
Mattioli
Michela
M
Fabris
Sonia
S
Nobili
Lucia
L
Intini
Daniela
D
Guerneri
Silvana
S
Todoerti
Katia
K
Zanella
Alberto
A
Deliliers
Giorgio Lambertenghi
GL
Lombardi
Luigia
L
Neri
Antonino
A
D000368:Aged; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D015850:Interleukin-6