Keyword: Minimal Residual Disease (MRD)

ABSTRACT: Minimal residual disease (MRD) has become a significant predictor of relapse and survival in acute myeloid leukemia (AML), indicating the extent of remission beyond traditional morphological evaluation. Although multicolor flow cytometry and quantitative PCR are essential methodologies in minimal residual disease identification, both are constrained by immunophenotypic variability, the necessity for stable molecular targets, and limited sensitivity. Advancements in next-generation sequencing (NGS) have revolutionized the minimal residual disease (MRD) field by enabling highly sensitive, mutation-driven identification of leukemic clones across a broad genomic landscape. Contemporary error-suppressed next-generation sequencing techniques—such as unique molecular identifiers, duplex sequencing, and single-molecule molecular inversion probes—have enhanced analytical sensitivity to the 10⁻⁵ to 10⁻⁶ range, enabling the detection of ultra-low-frequency variations with greater specificity. These techniques improve clinical risk classification, refine prognostication within genetically defined AML subtypes, and guide therapeutic options, including post-remission therapy, targeted inhibition, and the timing and intensity of allogeneic stem cell transplantation. Innovative applications, such as single-cell sequencing, cell-free DNA studies, and integrative multi-omic MRD evaluation, enhance the capabilities of genomics-based monitoring. Nonetheless, obstacles remain, such as differentiating cancer mutations from clonal hematopoiesis, standardizing analytical pipelines, establishing clinically relevant thresholds, and incorporating NGS MRD into standardized treatment protocols. This review encapsulates contemporary NGS methods for AML MRD diagnosis, assesses their clinical ramifications and constraints, and suggests future pathways necessary for comprehensive clinical integration. With advancements in the area, NGS-based MRD is set to become a pivotal element of precision-guided AML control.

ABSTRACT: Liquid biopsies have developed as a revolutionary technique in cancer diagnosis, treatment evaluation, and the detection of therapeutic resistance. Unlike traditional tissue biopsies, which are invasive and limited to a single temporal analysis, liquid biopsies offer a non-invasive, real-time evaluation of tumour dynamics through the analysis of biomarkers such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), exosomes, and microRNAs. This approach enables continuous monitoring of tumour advancement, allowing for the early detection of cancer, the tracking of minimal residual disease, and the identification of emerging resistance mutations. As cancers advance and acquire resistance to therapies, liquid biopsy provides critical information that enables clinicians to customise treatment strategies and improve outcomes. Despite challenges such as sensitivity limitations in early-stage cancers and the necessity for standardised testing protocols, technological advancements, including next-generation sequencing (NGS), CRISPR, and AI-driven analytics, are enhancing the precision and accessibility of liquid biopsies. Through ongoing validation and cost-reduction efforts, liquid biopsies are set to become essential to precision oncology, offering a transformative approach to cancer therapy that could improve patient outcomes and foster equitable healthcare globally.