文章：

聚（ADP-核糖）聚合酶1 mRNA水平与骨髓增生异常综合征的预后密切相关

Poly (ADP-ribose) polymerase 1 mRNA levels strongly correlate with the prognosis of myelodysplastic syndromes

原文发布日期：2017-02-17

DOI: 10.1038/bcj.2016.127

类型: Original Article

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英文摘要：

Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0.011) and the cytogenetic risk (P=0.008). In all cases, higher PARP1 levels were correlated with a higher risk category. Moreover, we found a significant survival disadvantage for patients with high PARP1 levels (median survival of 37.4 months versus ‘not reached’ for low PARP1 levels, P=0.0001, and a 5-year survival rate of 29.8 versus 88.9%, respectively). PARP1 mRNA levels were found to be the stronger predictor of survival in multivariate analysis. These correlations have never been reported in the past and may render PARP1 a prognostic factor to be incorporated in the current prognostic systems for MDS, also laying the basis for clinical trials evaluating PARP1 inhibitors in higher-risk MDS.

摘要翻译： 

聚腺苷二磷酸核糖聚合酶1（PARP-1）在DNA断裂修复中起核心作用，是恶性肿瘤治疗中一个颇具前景的靶点。我们通过SYBR green荧光定量PCR技术检测了74例骨髓增生异常综合征（MDS）患者骨髓中的PARP1 mRNA水平，并分析其与患者人口统计学特征、血液学指标及预后参数的相关性。研究发现PARP1 mRNA中位表达水平与MDS分型（基于2008/2016 WHO分类标准，P=0.005）及IPSS评分（P=0.002）显著相关，同时与IPSS-R评分（P=0.011）和细胞遗传学风险分级（P=0.008）存在关联。在所有病例中，较高PARP1水平均与更高风险分级呈正相关。值得注意的是，高PARP1水平患者存在显著生存劣势（中位生存期37.4个月vs低表达组"未达到"，P=0.0001；5年生存率分别为29.8% vs 88.9%）。多因素分析显示PARP1 mRNA水平是生存期的最强预测指标。这些关联性为首次报道，提示PARP1有望成为MDS现行预后系统中的新型预后因子，并为评估PARP1抑制剂在高危MDS中应用的临床试验奠定理论基础。

原文链接：

Poly (ADP-ribose) polymerase 1 mRNA levels strongly correlate with the prognosis of myelodysplastic syndromes