Researchers have demonstrated the feasibility and utility of circulating tumor DNA (ctDNA) as a minimally invasive biomarker for the diagnosis and monitoring of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

“Our study revealed that serial plasma-derived ctDNA assessments can reflect treatment response, survival, and clonal evolution in adult MDS and AML as a minimally invasive method, which warrant the prospective use of ctDNA as a biomarker in disease monitoring,” the researchers wrote.

In a letter to the editor of Clinical and Translational Medicine, the researchers explained they had detected 46 mutated genes with 135 mutations in both bone marrow DNA and plasma-derived ctDNA. Most (74.1%) of these mutations were found to be concordant between the 2 sources, indicating a high correlation in variant allele frequencies (VAFs) assessment.

Moreover, the researchers found that pretreatment ctDNA concentrations were strongly associated with tumor burden, highlighting the potential of ctDNA concentration as an effective prognostic biomarker in MDS and AML.

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In addition, dynamic monitoring of ctDNA during treatment showed promising results in predicting patient response and survival outcomes. Patients achieving complete response presented a significant decrease in VAF, whereas those with progressive disease exhibited an increase.

Post-treatment ctDNA positivity was associated with shorter progression-free survival and overall survival, while increased mean ctDNA VAF and concentration predicted poorer progression-free survival and overall survival.

In comparison with flow cytometry’s measurable residual disease results, ctDNA molecular residue detection was approximately 4 months earlier, suggesting the potential of ctDNA monitoring in detecting relapse at an earlier stage.

The study also revealed 2 main patterns of progression from MDS to secondary AML: linear and branched.

The research was based on targeted next-generation sequencing and involved 35 adult patients.


Zhou X, Lang W, Mei C, et al. Serial monitoring of circulating tumour DNA on clinical outcome in myelodysplastic syndromes and acute myeloid leukaemia. Clin Transl Med. Published online July 25, 2023. doi:10.1002/ctm2.1349