Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
División Patología Molecular, Instituto de Investigaciones Hematológicas "Mariano R. Castex", Academia Nacional de Medicina, Buenos Aires, Argentina.
Blood Cells Mol Dis. 2014 Feb-Mar;52(2-3):134-9. doi: 10.1016/j.bcmd.2013.10.002. Epub 2013 Nov 14.
The core complex of telomere-associated proteins, named the shelterin complex, plays a critical role in telomere protection and telomere length (TL) homeostasis. In this study, we have explored changes in the expression of telomere-associated genes POT1, TIN2, RAP1 and TPP1, in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). A total of 154 patients: 70 with MGUS and 84 with MM were studied. Real-time quantitative PCR was used to quantify gene expression. TL was evaluated by Terminal Restriction Fragments. Our data showed increased expression of POT1, TPP1, TIN2 and RAP1 in MM with respect to MGUS patients, with significant differences for POT1 gene (p=0.002). In MM, the correlation of gene expression profiles with clinical characteristics highlighted POT1 for its significant association with advanced clinical stages, high calcium and β2-microglobulin levels (p=0.02) and bone lesions (p=0.009). In multivariate analysis, POT1 expression (p=0.04) was a significant independent prognostic factor for overall survival as well as the staging system (ISS) (p<0.02). Our findings suggest for the first time the participation of POT1 in the transformation process from MGUS to MM, and provide evidence of this gene as a useful prognostic factor in MM as well as a possible molecular target to design new therapeutic strategies.
端粒相关蛋白的核心复合物，称为庇护体复合物，在端粒保护和端粒长度（TL）稳态中起着关键作用。在这项研究中，我们探讨了无意义单克隆丙种球蛋白血症（MGUS）和多发性骨髓瘤（MM）患者中端粒相关基因 POT1、TIN2、RAP1 和 TPP1 的表达变化。共研究了 154 例患者：70 例 MGUS 和 84 例 MM。实时定量 PCR 用于定量基因表达。端粒末端限制性片段（TRF）用于评估 TL。我们的数据显示，与 MGUS 患者相比，MM 中 POT1、TPP1、TIN2 和 RAP1 的表达增加，POT1 基因差异具有统计学意义（p=0.002）。在 MM 中，基因表达谱与临床特征的相关性突出了 POT1，因为它与晚期临床阶段、高钙和β2-微球蛋白水平（p=0.02）和骨病变（p=0.009）显著相关。在多变量分析中，POT1 表达（p=0.04）是总生存和分期系统（ISS）（p<0.02）的独立预后因素。我们的研究结果首次表明 POT1 参与了从 MGUS 向 MM 的转化过程，并为该基因作为 MM 有用的预后因素提供了证据，同时也为设计新的治疗策略提供了潜在的分子靶标。
