Faculdade de Medicina e Ciências Biomédicas (FMCB), Universidade do Algarve/Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Faro, Portugal.
Algarve Biomedical Center Research Institute (ABC-RI), Faro, Portugal.
JCO Clin Cancer Inform. 2024 Jul;8:e2300265. doi: 10.1200/CCI.23.00265.
AML is a hematologic cancer that is clinically heterogeneous, with a wide range of clinical outcomes. DNA methylation changes are a hallmark of AML but are not routinely used as a criterion for risk stratification. The aim of this study was to explore DNA methylation markers that could risk stratify patients with cytogenetically normal AML (CN-AML), currently classified as intermediate-risk.
DNA methylation profiles in whole blood samples from 77 patients with CN-AML in The Cancer Genome Atlas (LAML cohort) were analyzed. Individual 5'-cytosine-phosphate-guanine-3' (CpG) sites were assessed for their ability to predict overall survival. The output was validated using DNA methylation profiles from bone marrow samples of 79 patients with CN-AML in a separate data set from the Gene Expression Omnibus.
In the training set, using DNA methylation data derived from the 450K array, we identified 2,549 CpG sites that could potentially distinguish patients with CN-AML with an adverse prognosis () from those with a more favorable prognosis () independent of age. Of these, 25 CpGs showed consistent prognostic potential across both the 450K and 27K array platforms. In a separate validation data set, nine of these 25 CpGs exhibited statistically significant differences in 2-year survival. These nine validated CpGs formed the basis for a combined prognostic biomarker panel, which includes an 8-CpG Somatic Panel and the methylation status of cg23947872. This panel displayed strong predictive ability for 2-year survival, 2-year progression-free survival, and complete remission in the validation cohort.
This study highlights DNA methylation profiling as a promising approach to enhance risk stratification in patients with CN-AML, potentially offering a pathway to more personalized treatment strategies.
AML 是一种血液系统癌症，临床上具有异质性，临床结局广泛。DNA 甲基化改变是 AML 的一个标志，但不作为风险分层的标准。本研究旨在探索可对核型正常 AML（CN-AML）患者进行风险分层的 DNA 甲基化标志物，目前这些患者被归类为中危。
分析了来自癌症基因组图谱（LAML 队列）的 77 例 CN-AML 患者的全血样本中的 DNA 甲基化谱。评估了单个 5'-胞嘧啶-磷酸-鸟嘌呤-3'（CpG）位点预测总生存期的能力。使用来自基因表达综合数据库中 79 例 CN-AML 患者骨髓样本的 DNA 甲基化谱对结果进行验证。
在训练集中，使用 450K 阵列获得的 DNA 甲基化数据，我们确定了 2549 个 CpG 位点，这些 CpG 位点可以潜在地区分 CN-AML 患者的不良预后（）与预后较好的患者（），与年龄无关。其中 25 个 CpG 在 450K 和 27K 阵列平台上均显示出一致的预后潜力。在一个独立的验证数据集，这 25 个 CpG 中有 9 个在 2 年生存率上存在统计学差异。这 9 个验证 CpG 构成了一个综合预后生物标志物面板的基础，该面板包括一个 8-CpG 体细胞面板和 cg23947872 的甲基化状态。该面板在验证队列中对 2 年生存率、2 年无进展生存率和完全缓解具有很强的预测能力。
本研究强调 DNA 甲基化谱分析是增强 CN-AML 患者风险分层的一种很有前途的方法，可能为更个性化的治疗策略提供途径。
