麻省理工学院和哈佛大学的布罗德研究所Volker Hovestadt团队宣布他们提出了急性白血病的快速表观基因组分类。2025年9月22日出版的《自然—遗传学》发表了这项成果。

课题组人员开发了一个框架来分类急性白血病主题全基因组DNA甲基化分析。研究人员首先收集了一个全面的参考队列（n=2540个样本）并定义了38个甲基化类。在大多数情况下，基于甲基化的分类与标准病理谱系分类相匹配，并且除了遗传类别所捕获的异质性外，还揭示了异质性。利用这一参考文献，该课题组研究人员开发了一个神经网络（MARLIN；甲基化和人工智能引导的快速白血病亚型推断），用于从稀疏的DNA甲基化谱中对急性白血病进行分类。在纳米孔测序的回顾性队列中，26例中有25例的高置信度预测与常规诊断一致。急性白血病患者的实时MARLIN分类在5个病例中有5个提供了准确的预测，这些病例通常在2h样品接收。总之，研究组提出了一个框架快速急性白血病分类，补充和提高标准护理诊断。

据悉，急性白血病需要精确的分子分类和紧急治疗。然而，标准诊断测试是费时的，并不能捕获急性白血病异质性的全谱。

附：英文原文

Title: Rapid epigenomic classification of acute leukemia

Author: Steinicke, Til L., Benfatto, Salvatore, Capilla-Guerra, Maria R., Monteleone, Andre B., Young, Jonathan H., Shankar, Subha, Michaels, Phillip D., Tsai, Harrison K., Good, Jonathan D., Kreso, Antonia, van Galen, Peter, Schliemann, Christoph, Chen, Evan C., Griffin, Gabriel K., Hovestadt, Volker

Issue&Volume: 2025-09-22

Abstract: Acute leukemia requires precise molecular classification and urgent treatment. However, standard-of-care diagnostic tests are time-intensive and do not capture the full spectrum of acute leukemia heterogeneity. Here, we developed a framework to classify acute leukemia using genome-wide DNA methylation profiling. We first assembled a comprehensive reference cohort (n=2,540 samples) and defined 38 methylation classes. Methylation-based classification matched standard-pathology lineage classification in most cases and revealed heterogeneity in addition to that captured by genetic categories. Using this reference, we developed a neural network (MARLIN; methylation- and AI-guided rapid leukemia subtype inference) for acute leukemia classification from sparse DNA methylation profiles. In retrospective cohorts profiled by nanopore sequencing, high-confidence predictions were concordant with conventional diagnoses in 25 out of 26 cases. Real-time MARLIN classification in patients with suspected acute leukemia provided accurate predictions in five out of five cases, which were typically generated within 2h of sample receipt. In summary, we present a framework for rapid acute leukemia classification that complements and enhances standard-of-care diagnostics.

DOI: 10.1038/s41588-025-02321-z

Source: https://www.nature.com/articles/s41588-025-02321-z