Amplification of cyclin D1 gene in multiple myeloma: Clinical and prognostic relevance

Approximately 30% of myeloma patients express cyclin D1 RNA and protein. Th e low incidence of translocation t(11; 14) detected by conventional cytogen etics suggests that the up-regulation of cyclin D1 protein might result fro m other mechanisms as well as from gene amplification. Therefore, the frequ ency and the clinical and prognostic implications of cyclin D1 amplificatio n were examined. We highly purified myeloma cells from bone marrow by magne tic cell sorting and analysed 50 myelomas by fluorescence in situ hybridiza tion (FISH) using probes specific for cyclin D1 and 20 samples by immunoblo tting to detect cyclin D1 expression. The amplification of cyclin D1 gene w as found in 19 of 50 analysed patients and was associated with expression o f cyclin D1 protein. The amplification correlated significantly with the bo ne marrow infiltration, plasma cell morphology and labelling index as well as serum beta(2)-microglobulin, C-reactive protein (CRP) and creatinine lev els. In univariate analysis, the amplification of the cyclin D1 gene was a significantly unfavourable parameter with regard to overall survival (P = 0 .0064) and progression-free survival (P = 0.0005). In multivariate analysis , cyclin D1 amplification and serum beta 2-microglobulin were independent a nd well-suited parameters for predicting survival. The detection of cyclin D1 amplification seems to be of promising prognostic value in multiple myel oma.