DataSheet_1_Prognostic Prediction of Cytogenetically Normal Acute Myeloid Leukemia Based on a Gene Expression Model.pdf

Acute myeloid leukemia (AML) refers to a heterogeneous group of hematopoietic malignancies. The well-known European Leukemia Network (ELN) stratifies AML patients into three risk groups, based primarily on the detection of cytogenetic abnormalities. However, the prognosis of cytogenetically normal AML (CN-AML), which is the largest AML subset, can be hard to define. Moreover, the clinical outcomes associated with this subgroup are diverse. In this study, using transcriptome profiles collected from CN-AML patients in the BeatAML cohort, we constructed a robust prognostic Cox model named NEST (Nine-gEne SignaTure). The validity of NEST was confirmed in four external independent cohorts. Moreover, the risk score predicted by the NEST model remained an independent prognostic factor in multivariate analyses. Further analysis revealed that the NEST model was suitable for bone marrow mononuclear cell (BMMC) samples but not peripheral blood mononuclear cell (PBMC) samples, which indirectly indicated subtle differences between BMMCs and PBMCs. Our data demonstrated the robustness and accuracy of the NEST model and implied the importance of the immune dysfunction in the leukemogenesis that occurs in CN-AML, which shed new light on the further exploration of molecular mechanisms and treatment guidance for CN-AML.

急性髓系白血病（AML）是指一组异质性的造血系统恶性肿瘤。著名的欧洲白血病网络（ELN）主要依据细胞遗传学异常的检测，将AML患者划分为三个风险组。然而，作为最大AML亚组的细胞遗传学正常AML（CN-AML）的预后界定往往较为困难。此外，与该亚组相关的临床结果也呈现出多样性。在本研究中，我们利用收集自BeatAML队列中CN-AML患者的转录组谱，构建了一个名为NEST（九基因特征）的稳健预后Cox模型。NEST模型的可靠性在四个外部独立队列中得到验证。此外，NEST模型预测的风险评分在多变量分析中仍保持为独立的预后因素。进一步分析显示，NEST模型适用于骨髓单核细胞（BMMC）样本，而不适用于外周血单核细胞（PBMC）样本，这间接表明了BMMCs与PBMCs之间存在的细微差异。我们的数据展示了NEST模型的稳健性和准确性，并暗示了免疫功能障碍在CN-AML白血病发生发展中的重要性，为CN-AML的分子机制进一步探索和治疗指导提供了新的见解。