Establishment and characterization of a cytogenetically complex Chinese multiple myeloma-derived cell line with homozygous p53 deletion and cyclin E overexpression

Abstract

We describe the establishment and characterization of a new myeloma-derived cell line (MM17), originating from the sacral plasmacytoma of a 54-year-old Chinese woman diagnosed with multiple myeloma (MM). MM17 was confirmed morphologically and immunophenotypically to be clonal plasma cells positive for CD38 and CD138 and negative for EBV marker. Authenticity was confirmed using comparative genomic hybridization and DNA fingerprinting studies on bone marrow aspirate, sacral tumor tissue and MM17. Combined G-banding and multicolor fluorescence in situ hybridization analyses demonstrated a primarily hypodiploid karyotype with two sidelines sharing common stemline aberrations: +6, -7, -10, -13, -14, -17, -X, der(1;17)(q10;q10), t(2;7)(q23;q11.2), t(8;14)(q24;q32) and ins(16;1)(q13;?q22q41); and a number of hypertriploid cells. The involvement of p53 alteration and cyclin E overexpression, both with relevance to the induction of chromosomal instability, was investigated in MM17 and together with two other MM derived cell lines (U266 and IM-9) for cyclin E expression. Homozygous deletion of p53 gene hitherto not reported in MM, was detected. Both MM17 and U266 with complex cytogenetic aberrations demonstrated overexpression of cyclin E1 and E2, whereas IM-9 with a normal karyotype showed cyclin E2 but not E1 overexpression. These data suggested that E1 but not E2 overexpression was associated with chromosomal abnormalities observed in MM17 and U266, which provides the first supporting evidence for the link of cyclin E and chromosomal instability in MM. This is the first characterized Chinese MM-derived cell line with homozygous p53 deletion which may serve as a valuable in vitro system for studying MM pathogenesis particularly for Chinese.