PhD Scientific Days 2024

Budapest, 9-10 July 2024

Poster Session Q - Pathological and Oncological Sciences 2.

Digital Cytogenomics Improves Clinical Diagnostics of Acute Myeloid Leukemia


Anna Bekő1, Borbála Péterffy2, Katalin Csonka2, Lajos Hegyi2, Bettina Aranka Bohusné Barta2, Donát Alpár2, Csaba Bödör2
1: Department of Pathology and Experimental Cancer Research, Semmelweis University
2: HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University

Text of the abstract

Conventional karyotyping and fluorescence in situ hybridization (FISH) are widely used techniques in the clinical diagnostics of acute myeloid leukemia (AML). DNA-based optical genome mapping (OGM), a next-generation cytogenomic technique, allows for screening structural variants (SVs) and copy number alterations (CNAs) in a genome-wide manner with 500bp resolution in less than five days.
We aimed to test the feasibility, diagnostic applicability and added value of optical genome mapping in patients with AML and to compare OGM data with results obtained by conventional cytogenetic methods.
Diagnostic bone marrow samples from 50 adults with AML were collected from 11 Hungarian hematology centers. Basic molecular genetic analyses, karyotyping, FISH, and OGM were performed at Semmelweis University. For OGM, ultra-high molecular weight DNA isolation and sequence-specific fluorescent labeling were performed using optimized protocols, followed by imaging of individual molecules on the Saphyr platform (Bionano Genomics, San Diego, USA). Variant filtering and data interpretation were performed using the Bionano Access v1.8.1 software. The observed SVs and CNAs were compared with results obtained by karyotyping and FISH.
Overall, 95% concordance was observed between OGM data and results of conventional cytogenetic techniques, discordance was only observed in complex karyotypes (n=3). OGM successfully provided genome profiles in all 20 cases where the result of G-banding was unavailable. Initially, 28 patients were assigned to one of the AML with defining genetic abnormalities WHO subgroups. According to the OGM results, 6 cases, previously classified as ‘AML, defined by differentiation’, were re-classified into the ‘AML, myelodysplasia-related’ subgroup (n=5) and ‘AML with KMT2A rearrangement’ (n=1) subgroup. MECOM fusion was detected in 3 patients harboring complex rearrangements. Based on the European LeukemiaNet risk classification, 33 patients could be classified into prognostic subgroups by traditional methods, while 41 patients with OGM. Furthermore, by OGM KMT2A-PTD was observed in three patients with normal karyotype.
OGM allows the detection of clinically relevant aberrations in addition to those identified by conventional techniques. Therefore, it seems to be a promising test for routine cytogenomic diagnostics.