Optical genome mapping refines genomic risk stratification in therapy-related myeloid neoplasms and younger myelodysplastic syndromes
Accurate genomic characterization is essential for risk stratification in therapy-related myeloid neoplasms (t-MN) and younger myelodysplastic syndromes (yMDS), where chromosome banding analysis (CBA) has limited sensitivity. We analyzed 113 patients (48 t-MN, 65 yMDS) using optical genome mapping (OGM) integrated with CBA, targeted next-generation sequencing, and clinical data. OGM was interpretable in all cases and identified 134 additional genomic alterations (110% increase vs CBA), refining cytogenetic classification in 52.0% of abnormal karyotypes. OGM-detected relevant structural alterations in 9.8% of CBA-normal cases, including MDS 5q- reclassification. OGM-defined genomic groups showed significant differences in overall survival, confirmed by multivariable Cox analysis, and enabled identification of biallelic TP53 inactivation and chromoanagenesis events, enriched in TP53 -mutated cases and associated with inferior survival. Integration of OGM findings led to reclassification into higher-risk IPSS-R and IPSS-M categories in a subset of patients. OGM improves detection of genomic complexity and refines risk stratification in myeloid neoplasms.
Authors
- María Julia Montoro (ORCID: https://orcid.org/0000-0001-9532-7417)
- Juan José Rodríguez‐Sevilla (ORCID: https://orcid.org/0000-0002-4741-7925)
- Isabel Granada (ORCID: https://orcid.org/0000-0002-4275-0104)
- Estefanía Mancini (ORCID: https://orcid.org/0000-0002-7308-1273)
- Emili Cid (ORCID: https://orcid.org/0000-0002-5025-352X)
- Blanca Espinet (ORCID: https://orcid.org/0000-0002-4294-8145)
- Margarita Ortega (ORCID: https://orcid.org/0000-0002-1985-3965)
- Dolors Costa (ORCID: https://orcid.org/0000-0002-8276-3292)
- Oriol Calvete (ORCID: https://orcid.org/0000-0002-2623-2876)
- Mónica Del Rey (ORCID: https://orcid.org/0000-0002-1048-8148)
- Leonor Arenillas (ORCID: https://orcid.org/0000-0002-8176-7179)
- Lorea Chaparro‐González (ORCID: https://orcid.org/0009-0008-6806-9342)
- Raquel de Paz (ORCID: https://orcid.org/0000-0003-1627-0817)
- Esperanza Such
- Neus Torres-Hernández
- Lucía Ruiz Pérez-Hita
- Claudia Lozano
- Gonzalo Maortua (ORCID: https://orcid.org/0009-0003-7574-9462)
- Marta Salido
- Julia Mestre
- Francesc Solé
- Mar Mallo
- Sara García-Ávila
- Blanca Xicoy
- María Díez-Campelo
Institutions
- Hebron University (PS)
- Universitat Autònoma de Barcelona (ES)
- Universidad de Salamanca (ES)
- Hospital Universitario La Paz (ES)
- Hospital Universitari i Politècnic La Fe (ES)
- Josep Carreras Leukaemia Research Institute (ES)
- Hospital Clínic de Barcelona (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Hospital Del Mar (ES)
- Instituto de Investigación Biomédica de Salamanca (ES)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Instituto de Investigación Sanitaria La Fe (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2026-08-25
- DOI
- https://doi.org/10.1038/s41698-026-01671-z
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Generalitat de Catalunya
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- European Regional Development Fund