Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia
Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia
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DOI：
10.1038/s41408-020-0332-3
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发表时间：
2020-06-11
影响因子：
12.8
通讯作者：
Lehmann, Soren
中科院分区：
文献类型：
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作者：
Osterroos, Albin;Bjorklund, My;Lehmann, Soren
bb0 = 65岁急性髓性白血病（AML）患者治疗分层的相关分子工具缺乏。我们将临床数据与182例强化和姑息治疗患者的靶向DNA和全rna测序相结合，预测AML患者的完全缓解（CR）和生存期（bb0 = 65年）。强化治疗的npm1和didh2 （R172）突变患者的总生存期（OS）更长，而突变的tp53患者的CR率更低，OS更短。flt3 - itdandtp53突变预测姑息治疗患者的OS恶化。最能预测CR的基因表达水平与体细胞突变相结合，进行综合风险分层，我们使用beatAML队列进行外部验证。我们定义了一个高风险组，tp53突变患者的CR率为20%，而无tp53突变的zbtb7a和deepd1高表达的低风险患者的CR率为97%。没有这些标准的患者的CR率为54%（中危）。CR率的差异转化为显著的OS差异，优于ELN分层预测OS。结果提示，综合分子风险分层可以提高对CR和OS的预测，可用于指导老年AML患者的治疗。
Relevant molecular tools for treatment stratification of patients >= 65 years with acute myeloid leukemia (AML) are lacking. We combined clinical data with targeted DNA- and full RNA-sequencing of 182 intensively and palliatively treated patients to predict complete remission (CR) and survival in AML patients >= 65 years. Intensively treated patients withNPM1andIDH2(R172)mutations had longer overall survival (OS), whereas mutatedTP53conferred lower CR rates and shorter OS.FLT3-ITDandTP53mutations predicted worse OS in palliatively treated patients. Gene expression levels most predictive of CR were combined with somatic mutations for an integrated risk stratification that we externally validated using the beatAML cohort. We defined a high-risk group with a CR rate of 20% in patients with mutatedTP53, compared to 97% CR in low-risk patients defined by high expression ofZBTB7AandEEPD1withoutTP53mutations. Patients without these criteria had a CR rate of 54% (intermediate risk). The difference in CR rates translated into significant OS differences that outperformed ELN stratification for OS prediction. The results suggest that an integrated molecular risk stratification can improve prediction of CR and OS and could be used to guide treatment in elderly AML patients.