Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
Clin Lymphoma Myeloma Leuk. 2012 Feb;12(1):49-58. doi: 10.1016/j.clml.2011.09.217. Epub 2011 Nov 18.
Overexpression of cyclin D1 (CCND1) in the clonal plasma cells (PCs) of patients with systemic light chain amyloidosis (AL) has been shown to occur even in cases without t(11;14). Associations between CCND1 expression and the clonal PC disease that underlies AL and the clinical features that characterize AL have not been systematically evaluated.
To assess the significance of CCND1 expression in the pathophysiology of the clonal PC in AL, we evaluated CD138+ marrow PC from 16 newly diagnosed untreated patients by gene expression profiling (GEP) and performed a supervised analysis comparing clones that overexpressed CCND1 with those that did not. To assess the significance of CCND1 expression with respect to the clinical features of AL, we developed and validated a real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) method for quantitating expression of CCND1 in the CD138+ marrow PC cells from 53 newly diagnosed cases of AL.
In the analysis of GEP data, clones that overexpressed CCND1 also expressed significantly higher levels of endoplasmic reticulum protein processing genes such as SEL1L, Sec63, and PDIA6. In the analysis of RT-qPCR data, patients whose clones overexpressed CCND1 more often made only free light chains and fewer intact M-proteins, and also had a lower response rate to initial therapy. In multivariate analysis, CCND1 expression was an independent baseline predictor of survival in AL.
CCND1 expression is a feature of the clonal PC disease in AL that merits prospective evaluation.
系统性轻链淀粉样变性（AL）患者克隆浆细胞（PC）中 cyclin D1（CCND1）的过表达，即使在没有 t（11；14）的情况下也会发生。CCND1 表达与 AL 所基于的克隆 PC 疾病以及表征 AL 的临床特征之间的关联尚未系统评估。
为了评估 CCND1 表达在 AL 克隆 PC 病理生理学中的意义，我们通过基因表达谱（GEP）评估了 16 例新诊断未经治疗的患者的 CD138+骨髓 PC，并进行了一项有监督分析，比较了过表达 CCND1 的克隆与未过表达 CCND1 的克隆。为了评估 CCND1 表达与 AL 临床特征的意义，我们开发并验证了一种实时逆转录定量聚合酶链反应（RT-qPCR）方法，用于定量 53 例新诊断的 AL 患者的 CD138+骨髓 PC 细胞中 CCND1 的表达。
在 GEP 数据分析中，过表达 CCND1 的克隆还表达了显著更高水平的内质网蛋白加工基因，如 SEL1L、Sec63 和 PDIA6。在 RT-qPCR 数据分析中，过表达 CCND1 的克隆的患者通常仅产生游离轻链且较少产生完整的 M 蛋白，并且初始治疗的反应率也较低。在多变量分析中，CCND1 表达是 AL 患者生存的独立基线预测因子。
CCND1 表达是 AL 克隆 PC 疾病的一个特征，值得前瞻性评估。
