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| Home > Publications database > Rapid and reproducible karyotyping with long-read sequencing in patients with AML. |
| Home > Publications database > Rapid and reproducible karyotyping with long-read sequencing in patients with AML. |
| Journal Article | DKFZ-2026-02471 |
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2026
American Society of Hematology
Washington, DC
Abstract: Acute myeloid leukemia (AML) is characterized by recurrent chromosomal abnormalities that form the basis of the European LeukemiaNet risk classification and serve as essential determinants of prognosis and therapeutic decision-making. Conventional metaphase karyotyping remains the diagnostic gold standard for detecting these abnormalities; however, its utility is limited by longer turnaround times, often delaying critical clinical management. Here, we present a long-read, low-coverage whole-genome sequencing (lcWGS) approach using Oxford Nanopore Technology as a rapid and scalable alternative for cytogenetic profiling. A total of 100 diagnostic AML samples were analyzed, comprising 50 retrospectively selected patients with known adverse-risk cytogenetics and 50 prospectively enrolled patients with clinically defined de novo AML. LcWGS demonstrated robust analytical performance, identifying chromosomal aberrations with 93% sensitivity, specificity, and overall accuracy, respectively. Complex karyotypes were reliably detected, with an area under the curve of 0.971. Reproducibility was validated through replicate sequencing at 2 independent laboratories (R = 0.99). LcWGS-derived estimates of clone size showed moderate correlation with conventional cytogenetic assessments (R = 0.54). Patients with complex karyotypes identified by lcWGS exhibited significantly shorter overall and relapse-free survival, closely mirroring outcomes defined by conventional karyotyping and underscoring the value of lcWGS for risk stratification. The median turnaround time from sample receipt to bioinformatics interpretation was ∼34 hours, enabling delivery of actionable karyotype results within 72 hours. These findings establish lcWGS as a rapid, reproducible, and accurate platform for detecting clinically relevant chromosomal abnormalities, addressing a critical need for timely risk stratification and treatment initiation in AML.
Keyword(s): Humans (MeSH) ; Leukemia, Myeloid, Acute: genetics (MeSH) ; Leukemia, Myeloid, Acute: diagnosis (MeSH) ; Leukemia, Myeloid, Acute: mortality (MeSH) ; Karyotyping: methods (MeSH) ; Female (MeSH) ; Reproducibility of Results (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Chromosome Aberrations (MeSH) ; Aged (MeSH) ; Adult (MeSH) ; Prognosis (MeSH)
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