PhD Scientific Days 2026

Poster Session 1.D - Pathological and Oncological Sciences

Diagnostic Impact of Optical Genome Mapping in Acute Myeloid Leukemia

Name of the presenter

Bekő, Anna

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research, Semmelweis University

Authors

Anna Bekő¹, Balázs Kardos¹, Borbála Péterffy¹, Alex Hughes¹, Botond Timár¹, Alex Jenei¹, Gergő Papp¹, Lajos Hegyi¹, Donát Alpár¹, Csaba Bödör¹
1: Department of Pathology and Experimental Cancer Research, Semmelweis University

Text of the abstract

Introduction:
Comprehensive detection of clinically relevant structural variants (SVs), copy number alterations (CNAs), and gene mutations is essential for accurate classification and risk assessment in adult acute myeloid leukemia (AML). Conventional cytogenetics and targeted molecular assays identify recurrent abnormalities but may fail to resolve cryptic or complex genomic alterations. Optical genome mapping (OGM) enables genome-wide detection of SVs and CNAs, providing high-resolution structural profiling.

Aims:
To assess the feasibility and added value of OGM in the diagnostics of adult AML, and to identify clinically relevant patterns of co-occurrence and mutual exclusivity among genomic alterations.

Methods:
Diagnostic bone marrow samples from 100 adults with AML were analyzed using karyotyping and FISH. Molecular testing included standard screening for NPM1, FLT3-ITD, FLT3-TKD, CEBPA and IDH1 mutations, with targeted DNA-seq performed in a subset of patients. OGM was conducted using the Saphyr system (Bionano Genomics). Results were integrated across platforms. Statistical analyses were performed in GraphPad Prism v.8.0.2 and Python v.3.12.5 (p<0.05).

Results:
OGM generated a digital karyotype in all 100 cases, also including 25 patients with failed G-banding. Integration of OGM with targeted NGS refined the WHO classification in 13 patients, identifying MECOM rearrangements, myelodysplasia-related changes, and one NUP98 rearrangement. According to the ELN 2022 criteria, risk assessment based stratification changed in 15 patients (15%), predominantly shifting from intermediate to adverse risk. KMT2A partial tandem duplications were detected in eight cases and significantly co-occurred with AML defined by differentiation (p=0.004). In AML with RUNX1::RUNX1T1, KRAS mutations were significantly enriched (p=0.017). Additionally, a PRDM16::GATA2 fusion was identified in a patient sharing phenotypic features with MECOM-rearranged AML.

Conclusions:
OGM enables comprehensive detection of cryptic and complex structural alterations that may be missed by conventional methods. Integration of OGM with targeted NGS refined WHO classification in more than 10% of cases and altered the ELN 2022 risk stratification in 15% of patients.

Funding:
2023-2.1.2-KDP-2023-00016, SE250+ Excellence PhD Scholarship, Gedeon Richter Talentum Foundation’s scholarship