Liquid Biopsy and Epigenetic Signatures in AML, ALL, and CNS Tumors: Diagnostic and Monitoring Perspectives

Abstract

To deliver the most effective cancer treatment, clinicians require rapid and accurate diagnoses that delineate tumor type, stage, and prognosis. Consequently, minimizing the need for repetitive and invasive procedures like biopsies and myelograms, along with their associated risks, is a critical challenge. Non-invasive monitoring offers a promising avenue for tumor detection, screening, and prognostication. While the identification of oncogenes and biomarkers from circulating tumor cells or tissue biopsies is currently standard practice for cancer diagnosis and classification, accumulating evidence underscores the significant role of epigenetics in regulating stem cell fate, including proliferation, self-renewal, and malignant transformation. This highlights the importance of analyzing the methylome, exosomes, and circulating RNA for detecting cellular transformation. The development of diagnostic assays that integrate liquid biopsies with epigenetic analysis holds immense potential for revolutionizing tumor management by enabling rapid, non-invasive diagnosis, real-time monitoring, and personalized treatment decisions. This review covers current studies exploring the use of epigenetic regulation, specifically the methylome and circulating RNA, as diagnostic tools derived from liquid biopsies. This approach shows promise in facilitating the differentiation between primary central nervous system lymphoma and other central nervous system tumors and may enable the detection and monitoring of acute myeloid/lymphoid leukemia. We also discuss the current limitations hindering the rapid clinical translation of these technologies.

Keywords: PCNSL; circulating RNA; early diagnosis; epigenetic; leukemia; liquid biopsy; lymphoma; methylome.

Figure 1

Liquid biopsy is combined with epigenomic profiling as a biomarker approach for cancer detection and monitoring. Schematic illustration of experimental and bioinformatics procedures: Blood samples or cerebrospinal fluid are collected from cancer patients or non-cancer control donors. Circulating RNA or cfDNA is then extracted from the participant’s sample, and the cfDNA is subjected to cytosine conversion and NGS analysis. Transcriptomic profiling of circulating mRNA and quantification of methylation-specific signals (e.g., methylated fragment ratios) are performed. A multimodal ensemble classifier integrates molecular features from both transcriptomic and epigenomic datasets to generate a probabilistic score indicating the presence of malignant transformation.

Figure 2

Innovative Diagnostics for Leukemia and Brain Tumors: The use of liquid biopsies (plasma, serum, and CSF), combined with methylated DNA and circulating mRNA as epigenetic markers for diagnosing leukemia (ALL and AML) and brain tumors, offers less invasive, faster alternatives to traditional diagnostics. This approach improves early diagnosis and detection of relapse and treatment decisions, ultimately enhancing patient outcomes.