Liquid Biopsy for Measurable Residual Disease in Acute Myeloid Leukemia
What cfDNA adds to AML MRD monitoring: lessons from a peripheral-blood study
Measurable residual disease (MRD) is an important prognostic marker in acute myeloid leukemia (AML), and bone marrow remains the standard specimen. Repeated aspiration is invasive, and each sample captures only a fraction of the marrow compartment. A study led by Hospital Universitario 12 de Octubre in Madrid asked what peripheral-blood liquid biopsy can add.
Study Overview
Published in Frontiers in Immunology in 2024, the work was conducted by Noemí Álvarez as first author, with Rosa Ayala and Santiago Barrio sharing senior scientific leadership, in collaboration with Altum Sequencing. Of 24 patients initially included, 20 were analyzed, with 74 peripheral-blood follow-up samples (39 circulating tumor cell and 35 cfDNA samples). Variants identified with a 42-gene myeloid panel at diagnosis were tracked at ~500,000× depth per amplicon, using marker-specific noise control and an MRD positivity threshold of 10⁻⁴.
cfDNA and CTCs Show Strong Agreement
Across paired observations, cfDNA and CTC measurements were highly correlated (R² = 0.927, p < 0.001). In most pairs, the signal in cfDNA was higher, with a median of 0.0035 versus 0.0007 in CTCs (p = 0.048). Timing still matters: early after treatment, cfDNA may contain DNA released from dying cells, while CTCs represent viable cells.
Different Compartments, Different Information
Compared with bone-marrow flow cytometry, peripheral-blood cfDNA gave concordant results in 12 of 20 patients and discordant results in 8, with a lower quantitative correlation (R² = 0.311, p = 0.016). The two approaches analyze different specimens, biological fractions and detection principles, so discordance can carry biological information.
Choosing the Right Biomarker
Detecting a mutation at diagnosis does not automatically make it a reliable MRD marker. An IDH2 p.R140Q variant stayed close to 50% at diagnosis and follow-up, reflecting a background clone rather than active leukemia. In another patient, a RUNX1 variant became undetectable by liquid biopsy while flow cytometry remained positive, and the patient later relapsed. The authors recommend tracking several markers and evaluating their kinetics over time.
From Published Evidence to Altum TRACKseq
The publication describes the methodology as LiqBio-MRD. Its core strategy of patient-specific biomarker selection, ultra-deep sequencing, marker-specific noise control and longitudinal tracking is aligned with the principles implemented in Altum TRACKseq. This is a current technology mapping and does not rename the assay used in the 2024 study.
Limitations and Future Directions
This was a small, heterogeneous cohort, and the study was not designed to establish clinical decision thresholds or prove superiority over bone-marrow MRD. Larger prospective studies, standardization and defined time points will be needed before cfDNA-based MRD can enter routine AML management.
Download the Full Whitepaper
Our new whitepaper, Liquid Biopsy for Measurable Residual Disease in Acute Myeloid Leukemia, explores cfDNA, circulating tumor cells and biomarker selection for longitudinal molecular monitoring.
Designing an AML MRD study? Talk to Altum Sequencing about tumor-informed biomarker strategy and longitudinal monitoring in translational and clinical research.
Altum Sequencing is a Madrid-based precision oncology company spun off from Hospital Universitario 12 de Octubre, developing ctDNA-based liquid biopsy technology for cancer monitoring and MRD detection.
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