Challenges facing minimal residual disease testing for acute myeloid leukemia and promising strategies to overcome them

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.

KEYWORDS:

• Minimal/measurable residual disease
• acute myeloid leukemia
• challenges
• technique
• relapse

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.

Additional information

Funding

This work was partly supported by grants from the Beijing Municipal Science and Technology Commission (No. Z221100007422008) and the National Key Research and Development Program of China (No. 2022YFA1103300).