Abstract
Detection of measurable residual disease (MRD) is of significant value in the management
of acute myeloid leukemia (AML) patients. Along with multicolor flowcytometry (MFC),
molecular techniques form an integral tool in AML MRD detection. Multiple studies
have reiterated the role of molecular MRD evaluation in AML at defined timepoints
during the course of therapy, helping in risk stratification, prediction of relapse,
and as guide for pre-emptive therapy. The latest World Health Organization (WHO) classification
(WHO-HEME5) has refined the classification of AML bringing forth newer entities defined
by molecular abnormalities, especially fusions. AML is a clonally heterogeneous disease
characterized by a spectrum of multiple molecular abnormalities including gene mutations
and fusions. Accordingly, the molecular methods employed are also diverse and need
robust technical standardization in clinical laboratories. Real-time quantitative
polymerase chain reaction (PCR), digital PCR, and next-generation sequencing (NGS)
are the major molecular platforms for AML MRD. The European LeukemiaNet (ELN) MRD
Working Party consensus document recently updated in 2021 for the first time has reflected
on the technical recommendations for NGS MRD in AML and stressed the value of an integrated
approach. It is, therefore, desirable for physicians, scientists, and pathologists
alike to thoroughly understand these molecular methods for appropriate utilization
and interpretation. In this article, we discuss the various facets of molecular methods
for MRD detection in AML including technical requirements, advantages, drawbacks,
and applications.
Keywords
molecular MRD - error corrected next-generation sequencing - measurable residual disease
