Molecular Minimal Residual Disease Detection in Acute Myeloid Leukemia
Christian M Vonk1, Adil S A Al Hinai1,2, Diana Hanekamp1,3
1Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 CN Rotterdam, The Netherlands.
Abstract:
Initial induction chemotherapy to eradicate the bulk of acute myeloid leukemia (AML) cells results in complete remission (CR) in the majority of patients. However, leukemic cells persisting in the bone marrow below the morphologic threshold remain unaffected and have the potential to proliferate and re-emerge as AML relapse. Detection of minimal/measurable residual disease (MRD) is a promising prognostic marker for AML relapse as it can assess an individual patients' risk profile and evaluate their response to treatment. With the emergence of molecular techniques, such as next generation sequencing (NGS), a more sensitive assessment of molecular MRD markers is available. In recent years, the detection of MRD by molecular assays and its association with AML relapse and survival has been explored and verified in multiple studies. Although most studies show that the presence of MRD leads to a worse clinical outcome, molecular-based methods face several challenges including limited sensitivity/specificity, and a difficult distinction between mutations that are representative of AML rather than clonal hematopoiesis. This review describes the studies that have been performed using molecular-based assays for MRD detection in the context of other MRD detection approaches in AML, and discusses limitations, challenges and opportunities.
Insights
Detecting minimal residual disease (MRD) in acute myeloid leukemia (AML) using molecular assays like NGS is crucial for predicting relapse. However, challenges in sensitivity and specificity remain.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Acute myeloid leukemia (AML) treatment often achieves complete remission (CR) but residual cells can cause relapse.
- Minimal/measurable residual disease (MRD) detection is vital for prognosis and treatment response assessment in AML.
- Molecular techniques, particularly next-generation sequencing (NGS), offer enhanced sensitivity for MRD detection.
Purpose of the Study:
- To review studies on molecular assays for MRD detection in AML.
- To discuss the association between molecular MRD and AML relapse/survival.
- To highlight the limitations and challenges of current molecular MRD detection methods.
Main Methods:
- Review of existing literature on molecular MRD detection in AML.
- Analysis of studies employing techniques like NGS for MRD assessment.
- Comparison of molecular MRD detection with other existing approaches.
Main Results:
- Molecular MRD detection, especially via NGS, shows strong correlation with AML relapse and poorer survival outcomes.
- Studies confirm the prognostic value of molecular MRD in AML patients.
- Despite advancements, molecular assays face challenges including sensitivity, specificity, and differentiating AML mutations from clonal hematopoiesis.
Conclusions:
- Molecular-based MRD detection is a powerful tool in AML management, offering prognostic insights.
- Addressing limitations in sensitivity, specificity, and distinguishing true AML mutations is essential for wider clinical adoption.
- Further research and standardization are needed to optimize molecular MRD assays for AML.
More Related Videos
09:01Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
06:33Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
Published on: November 10, 2023