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. 2024 Jun 13:15:1252258.
doi: 10.3389/fimmu.2024.1252258. eCollection 2024.

Detection of minimal residual disease in acute myeloid leukemia: evaluating utility and challenges

Noemí Álvarez  1   2 , Alejandro Martín  2   3 , Sara Dorado  3   4 , Rafael Colmenares  1 , Laura Rufián  1   3 , Margarita Rodríguez  1   3 , Alicia Giménez  1 , Laura Carneros  1 , Ricardo Sanchez  1 , Gonzalo Carreño  1 , Inmaculada Rapado  1 , Yanira Heredia  3 , Joaquín Martínez-López  1   2   5   6 , Santiago Barrio  1   2   3 , Rosa Ayala  1   2   5   6
Affiliations

Detection of minimal residual disease in acute myeloid leukemia: evaluating utility and challenges

Noemí Álvarez et al. Front Immunol. .

Abstract

This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area.

Keywords: AML; Leukaemia; MRD; NGS; liquid biopsy; multiparametric flow cytometry.

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Conflict of interest statement

Authors AM, SD, LR, MR, YH, and SB were employed by the company Altum Sequencing Co. RA, JM-L, and SB are equity shareholders of Altum Sequencing Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Correlation between CTCs and cfDNA in paired samples. (B) Correlation between the MRD study by NGS and by MFC.
Figure 2
Figure 2
(A) MRD signal by NGS in cfDNA vs. CTCs. (B) Examples of patients where higher sensitivity was observed in cfDNA samples compared to CTCs samples. The X-axis represents the date on which the sample was obtained and the Y-axis represents the Variant Allele Frequency (VAF) of the sample.
Figure 3
Figure 3
(A) Patient in whom the importance of choosing a good marker was shown. (B) Patient in whom the sensitivity of the marker was significantly reduced. (C, D) Patients in whom there was no clearance of the marker after treatment.
See this image and copyright information in PMC

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