Circulating biomarkers in leukemia

Area of Science:

• Hematology
• Oncology
• Molecular Diagnostics

Background:

• Liquid biopsy analyzes circulating biomarkers (cfDNA, ctDNA, miRNAs, EVs) for real-time insights into hematologic malignancies.
• Blood-based assays offer serial sampling advantages over bone-marrow biopsy for capturing temporal changes and heterogeneity.

Purpose of the Study:

• To review current technologies, clinical applications, and translational opportunities for circulating biomarkers in leukemia.
• To discuss challenges hindering the clinical implementation of these biomarkers.

Main Methods:

• Review of current high-throughput sequencing and digital PCR technologies for biomarker detection.
• Analysis of clinical studies correlating circulating tumor DNA (ctDNA) kinetics with patient outcomes.
• Evaluation of barriers to assay standardization and interpretation of low-frequency variants.

Main Results:

• Advances in technology improve sensitivity for detecting minimal residual disease (MRD), clonal evolution, and resistance mutations.
• ctDNA kinetics correlate with progression-free and overall survival in lymphoid and myeloid malignancies, suggesting its potential as an early surrogate of treatment benefit.
• Sensitivity varies by disease biology, necessitating combination with marrow-based MRD and leukocyte sequencing pending standardization.

Conclusions:

• Circulating biomarkers hold promise for personalized treatment decisions and early relapse detection in hematologic malignancies.
• Standardization of assays, understanding biological variability, and robust interpretation frameworks are crucial for clinical integration.
• Further prospective standardization is needed before widespread adoption, especially for ctDNA, in combination with traditional methods.