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Genomic DNA-based measurable residual disease monitoring in pediatric acute myeloid leukemia: unselected consecutive cohort study
M. Zaliova, J. Zuna, L. Winkowska, I. Janotova, J. Skorepova, J. Lukes, C. Meyer, R. Marschalek, Z. Novak, J. Domansky, J. Stary, L. Sramkova, J. Trka
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Open Access Digital Library
od 1997-01-01
Nursing & Allied Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- akutní myeloidní leukemie * diagnóza genetika terapie MeSH
- dítě MeSH
- genomika MeSH
- kohortové studie MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- prognóza MeSH
- průtoková cytometrie MeSH
- recidiva MeSH
- reziduální nádor diagnóza genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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 × 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.
Citace poskytuje Crossref.org
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- $a Zaliova, Marketa $u CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic. marketa.zaliova@lfmotol.cuni.cz $u Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. marketa.zaliova@lfmotol.cuni.cz $u University Hospital Motol, Prague, Czech Republic. marketa.zaliova@lfmotol.cuni.cz $1 https://orcid.org/0000000216397124 $7 xx0074371
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