ABSTRACT
Introduction
Minimal residual disease (MRD) has been an important biomarker for relapse prediction and treatment choice in patients with acute myeloid leukemia (AML). False-positive or false-negative MRD results due to the low specificity and sensitivity of techniques such as multiparameter flow cytometry (MFC), real-time quantitative polymerase chain reaction, and next-generation sequencing, as well as the biological characteristics of residual leukemia cells, including antigen shift, clone involution, heterogeneous genome of the blast cells, and lack of specific targets, all restrict the clinical use of MRD.
Areas covered
We summarized the challenges of the techniques for MRD detection, and their application in the clinical setting. We also discussed strategies to overcome these challenges, such as the MFC MRD method based on leukemia stem cells, single-cell DNA sequencing or single-cell RNA sequencing for the investigation of biological characteristics of residual leukemia cells, and the potential of omics techniques for MRD detection. We further noted out that prospective clinical trials are needed to answer clinical questions related to MRD in patients with AML.
Expert opinion
MRD is an important biomarker for individual therapy of patients with AML. In the future, it is important to increase the specificity and sensitivity of the detection techniques.
Article highlights
Minimal residual disease (MRD) has been successfully used for relapse prediction and treatment choice in patients with acute myeloid leukemia (AML).
False-positive or false-negative MRD results due to the insufficient specificity and sensitivity of the residual disease testing hamper recurrence prediction.
In clinical setting, the best time point for MRD evaluation and the optimal cutoff value of MRD for leukemia relapse prediction in patients with AML remain to be investigated.
Elucidating the biological characteristics of residual leukemia cells and establishing novel techniques, such as leukemia stem cell-based MRD assay and omics technology for MRD, may contribute to increase the specificity and sensitivity of the residual disease testing.
Prospective, well-designed, multicenter trials should be performed to overcome the challenges in the clinical setting.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.
Acknowledgments
We thank LetPub (www.letpub.com) for assistance in editing this manuscript.