Molecular MRD Assessment in Acute Myeloid Leukemias

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.