Circulating biomarkers in leukemia.

Liquid biopsy is a minimally invasive approach that analyzes circulating biomarkers, including cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and extracellular vesicles (EVs), to provide real-time information about the genetic and epigenetic state of hematologic malignancies. Compared with bone-marrow biopsy, blood-based assays enable serial sampling and can better capture temporal changes and spatial heterogeneity. Advances in high-throughput sequencing and digital PCR have improved detection sensitivity for minimal residual disease (MRD), clonal evolution, and resistance mutations. Integration of circulating biomarkers into clinical care may support personalized treatment decisions and earlier relapse detection, but barriers remain: assay standardization, biological variability, and interpretation of low-frequency variants. Interpretation of existing clinical studies suggests that ctDNA kinetics (for example, early on-treatment clearance vs persistent detection) frequently correlate with progression-free and overall survival (OS) in lymphoid and myeloid malignancies, supporting ctDNA as a candidate early surrogate of treatment benefit; however, sensitivity differs by disease biology (marrow-predominant AML vs nodal lymphomas) and therefore ctDNA should be used in combination with marrow-based MRD and leukocyte sequencing until prospective standardization is established. This review summarizes current technologies, clinical applications, and translational opportunities for circulating biomarkers in leukemia and discusses outstanding challenges for clinical implementation.