New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFB-MYH11+ acute myeloid leukemia based on quantification of fusion transcripts

New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFB-MYH11+ acute myeloid leukemia based on quantification of fusion transcripts
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DOI:
10.1182/blood-2003-03-0880
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发表时间:
2003-10-15
期刊:
影响因子:
20.3
通讯作者:
Kern, W
Kern, W
中科院分区:
医学1区
文献类型:
--
作者:
Schnittger, S;Weisser, M;Kern, W

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为了评估定量PML-RARA、AML 1-ETO和CBFB-MYH 11融合转录本表达的预后意义,使用实时聚合酶链反应分析了349例诊断时的此类患者的骨髓样本和142例治疗期间的522例样本(总分析,n = 859;随访样本的中位数,4/患者;评估的中位数持续时间,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体和无事件生存期相关。通过合并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,将3个急性髓性白血病亚组中的100%EFS组与显著更差的组(P < .0001)区分开来。8名患者在随访期间表现出表达水平增加,并且全部复发。总之,治疗失败的高风险患者可以通过诊断时高水平的融合基因表达或在治疗的前3至4个月内肿瘤缩小小于3个对数来识别。通过结合这2个检查点的转录比,建立了一个新的强大的预后评分。(C)2003年,美国血液学会。
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. (C) 2003 by The American Society of Hematology.