文章：

在阿扎胞苷治疗的MDS或AML患者队列中，通过基于SNP阵列的分子核型测定的总基因组改变可预测总生存率

Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine

原文发布日期：2013-11-01

DOI: 10.1038/bcj.2013.52

类型: Original Article

开放获取: 是

英文摘要：

Metaphase cytogenetics (MC) has a major role in the risk stratification of patients with myelodysplastic syndromes (MDSs) and can affect the choice of therapies. Azacitidine (AZA) has changed the outcome of patients with MDS or acute myeloid leukemia (AML) unfit for intensive chemotherapy. Identification of patients without the benefit of AZA would allow AZA combination or other drugs in first-line treatments. New whole-genome scanning technologies such as single nucleotide polymorphism microarray (SNP-A)-based molecular karyotyping (MK) improve the risk stratification in MDS and AML. Maintenance of genomic integrity is less than three megabases (Mbs) total disruption of the genome correlated with better overall survival (OS) in patients with lower-risk MDS. In this SNP-A study, we aimed at defining a cutoff value for total genomic copy number (CN) alterations (TGA) influencing the median OS in a cohort of 51 higher-risk MDS/AML patients treated with AZA. We observed that the relative risk of worse OS increased >100 Mb of TGA, as detected by SNP-A-based MK (8 and 15 months respectively, P=0.02). Our data suggest that precise measurement of TGA could provide predictive information in poor and very poor revised International Prognostic Scoring system (IPSS-R) patients treated with AZA.

摘要翻译： 

中期细胞遗传学（MC）在骨髓增生异常综合征（MDS）患者的风险分层中具有重要作用，并可影响治疗方案的选择。阿扎胞苷（AZA）改变了不适合强化化疗的MDS或急性髓系白血病（AML）患者的预后。识别无法从AZA治疗中获益的患者有助于在一线治疗中采用AZA联合方案或其他药物。新型全基因组扫描技术，如基于单核苷酸多态性微阵列（SNP-A）的分子核型分析（MK），可改善MDS和AML的风险分层。基因组完整性维持（即总基因组破坏小于3兆碱基）与较低风险MDS患者更好的总生存期（OS）相关。本项SNP-A研究旨在确定总基因组拷贝数（CN）改变（TGA）的临界值，该值影响51例接受AZA治疗的高危MDS/AML患者的中位OS。我们观察到，通过SNP-A基MK检测到TGA超过100 Mb时，较差OS的相对风险增加（分别为8个月和15个月，P=0.02）。我们的数据表明，TGA的精确测量可为接受AZA治疗的国际预后评分系统修订版（IPSS-R）评分为差和极差的患者提供预测信息。

原文链接：

Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine