Genomic DNA-based measurable residual disease monitoring in pediatric acute myeloid leukemia: unselected consecutive cohort study

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Authors

ZALIOVA Marketa ZUNA Jan WINKOWSKA Lucie JANOTOVA Iveta SKOREPOVA Justina LUKES Julius MEYER Claus MARSCHALEK Rolf NOVAK Zbynek DOMANSKÝ Jiří STARY Jan SRAMKOVA Lucie TRKA Jan

Year of publication 2024
Type Article in Periodical
Magazine / Source Leukemia
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.nature.com/articles/s41375-023-02083-9
Doi http://dx.doi.org/10.1038/s41375-023-02083-9
Keywords pediatric acute myeloid leukemia; residual disease monitoring
Attached files
Description Measurable residual disease (MRD) monitoring in childhood acute myeloid leukemia (AML) is used to assess response to treatment and for early detection of imminent relapse. In childhood AML, MRD is typically evaluated using flow cytometry, or by quantitative detection of leukemia-specific aberrations at the mRNA level. Both methods, however, have significant limitations. Recently, we demonstrated the feasibility of MRD monitoring in selected subgroups of AML at the genomic DNA (gDNA) level. To evaluate the potential of gDNA-based MRD monitoring across all AML subtypes, we conducted a comprehensive analysis involving 133 consecutively diagnosed children. Integrating next-generation sequencing into the diagnostic process, we identified (presumed) primary genetic aberrations suitable as MRD targets in 97% of patients. We developed patient-specific quantification assays and monitored MRD in 122 children. The gDNA-based MRD monitoring via quantification of primary aberrations with a sensitivity of at least 10-4 was possible in 86% of patients; via quantification with sensitivity of 5 x 10-4, of secondary aberrations, or at the mRNA level in an additional 8%. Importantly, gDNA-based MRD exhibited independent prognostic value at early time-points in patients stratified to intermediate-/high-risk treatment arms. Our study demonstrates the broad applicability, feasibility, and clinical significance of gDNA-based MRD monitoring in childhood AML.
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