Hoechtlen-Vollmar W, Menzel G, Bartl R, Lamerz R, Wick M, Seidel D
Institute of Clinical Chemistry, Ludwig Maximilians Universitaet Muenchen, Grosshadern, Munich, Germany.
Br J Haematol. 2000 Apr;109(1):30-8. doi: 10.1046/j.1365-2141.2000.02007.x.
Approximately 30% of myeloma patients express cyclin D1 RNA and protein. The low incidence of translocation t(11; 14) detected by conventional cytogenetics suggests that the up-regulation of cyclin D1 protein might result from other mechanisms as well as from gene amplification. Therefore, the frequency and the clinical and prognostic implications of cyclin D1 amplification were examined. We highly purified myeloma cells from bone marrow by magnetic cell sorting and analysed 50 myelomas by fluorescence in situ hybridization (FISH) using probes specific for cyclin D1 and 20 samples by immunoblotting to detect cyclin D1 expression. The amplification of cyclin D1 gene was found in 19 of 50 analysed patients and was associated with expression of cyclin D1 protein. The amplification correlated significantly with the bone marrow infiltration, plasma cell morphology and labelling index as well as serum beta2-microglobulin, C-reactive protein (CRP) and creatinine levels. 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 beta2-microglobulin were independent and well-suited parameters for predicting survival. The detection of cyclin D1 amplification seems to be of promising prognostic value in multiple myeloma.
约30%的骨髓瘤患者表达细胞周期蛋白D1 RNA和蛋白。传统细胞遗传学检测到的t(11;14)易位发生率较低，提示细胞周期蛋白D1蛋白的上调可能是由基因扩增以外的其他机制引起的。因此，研究了细胞周期蛋白D1扩增的频率及其临床和预后意义。我们通过磁珠细胞分选从骨髓中高度纯化骨髓瘤细胞，并用细胞周期蛋白D1特异性探针通过荧光原位杂交(FISH)分析了50例骨髓瘤，通过免疫印迹检测细胞周期蛋白D1表达分析了20个样本。在50例分析患者中，有19例发现细胞周期蛋白D1基因扩增，且与细胞周期蛋白D1蛋白的表达相关。扩增与骨髓浸润、浆细胞形态和标记指数以及血清β2-微球蛋白、C反应蛋白(CRP)和肌酐水平显著相关。单因素分析显示，细胞周期蛋白D1基因扩增在总生存期(P = 0.0064)和无进展生存期(P = 0.0005)方面是一个显著不利的参数。多因素分析显示，细胞周期蛋白D1扩增和血清β2-微球蛋白是预测生存的独立且合适的参数。细胞周期蛋白D1扩增的检测在多发性骨髓瘤中似乎具有良好的预后价值。
