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基于融合转录本定量的新评分系统预测PML-RARA+、AML1-ETO+或CBFBMYH11+急性髓系白血病的预后

New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts.

作者信息

Schnittger Susanne, Weisser Martin, Schoch Claudia, Hiddemann Wolfgang, Haferlach Torsten, Kern Wolfgang

机构信息

Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany.

出版信息

Blood. 2003 Oct 15;102(8):2746-55. doi: 10.1182/blood-2003-03-0880. Epub 2003 Jul 3.

Abstract

To evaluate the prognostic significance of quantitative PML-RARA, AML1-ETO, and CBFB-MYH11 fusion transcript expression, real-time polymerase chain reaction was used to analyze bone marrow samples of 349 such patients at diagnosis and 522 samples of 142 patients also during therapy (total analyses, n = 859; median number of follow-up samples, 4/patient; median duration of assessment, 12 months). Lower expression levels at diagnosis correlated with better overall and event-free survival in all 3 leukemia subtypes. By combining the median expression ratio after consolidation therapy and the 75th percentile of the expression ratio at diagnosis, a new score was established that separates a group with 100% EFS from a significantly worse group (P <.0001) in each of the 3 acute myeloid leukemia subgroups. Eight patients showed increasing levels of expression during follow-up and all had relapse. In conclusion, patients at high risk for treatment failure can be identified by high levels of fusion gene expression at diagnosis or less than 3 logs of tumor reduction during the first 3 to 4 months of therapy. By combining the transcription ratios at these 2 checkpoints, a new powerful prognostic score has been established.

摘要

为评估定量PML-RARA、AML1-ETO和CBFB-MYH11融合转录本表达的预后意义,采用实时聚合酶链反应分析了349例此类患者诊断时的骨髓样本以及142例患者治疗期间的522份样本(总计分析样本859份;每位患者随访样本中位数为4份;评估中位持续时间为12个月)。在所有3种白血病亚型中,诊断时较低的表达水平与较好的总生存期和无事件生存期相关。通过结合巩固治疗后的中位表达率和诊断时表达率的第75百分位数,建立了一个新的评分系统,该系统在3个急性髓系白血病亚组中均能将无事件生存期为100%的一组与明显较差的一组区分开来(P <.0001)。8例患者在随访期间表达水平升高,均复发。总之,治疗失败高风险患者可通过诊断时融合基因高表达或治疗前3至4个月内肿瘤缩小少于3个对数来识别。通过结合这两个检查点的转录率,建立了一个新的强大的预后评分系统。

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