Comprehensive genetic characterization of adult BCR::ABL1-negative B-ALL by Optical Genome Mapping and Targeted NGS
Adult B-cell precursor acute lymphoblastic leukemia (B-ALL) is genetically heterogeneous, comprising numerous subtypes. Standard methods leave many patients unclassified, and routine implementation of whole-transcriptome sequencing (WTS) or whole-genome sequencing (WGS) is limited. We evaluated a combined workflow of Optical Genome Mapping (OGM) and targeted next-generation sequencing (t-NGS) for genetic characterization of 100 adult BCR::ABL1-negative B-ALL patients enrolled in PETHEMA-LAL-19. This approach was compared with protocol genetic testing. The integration of OGM and t-NGS enabled the classification of 84% of BCR::ABL1-negative patients into 15 distinct subtypes, reducing the proportion of B-other/unclassified case from 50% to 16%. OGM was useful in identifying BCR::ABL1-like (26% of cases), associated with post-induction minimal residual disease (MRD) positivity (72% vs. 34%, p=0.0011), while t-NGS contributed to the detection of mutation-defined subtypes (PAX5 P80R and PAX5alt), correlated with MRD negativity (91% vs. 51%, p=0.012). OGM and t-NGS identified genetic patterns of certain subtypes, including a higher prevalence of IKZF1plus in BCR::ABL1-like (62% vs. 12%, p<0.001), JAK-STAT mutations only in patients with CRLF2-rearrangements and a high prevalence of PAX5-biallelic events (92% vs. 2%, p<0.001) in PAX5-subtypes. Therefore, the integration of OGM and t-NGS represents a feasible approach that enables comprehensive genetic characterization of adult BCR::ABL1-negative B-ALL, supporting its implementation in routine diagnostic workflows.
Authors
- Irene Rodríguez (ORCID: https://orcid.org/0000-0001-8016-4459)
- Carolina Martínez‐Laperche (ORCID: https://orcid.org/0000-0001-6802-3485)
- Alberto Hernández‐Sánchez (ORCID: https://orcid.org/0000-0002-6601-3096)
- Blanca Espinet Solà
- Mireia Morgades (ORCID: https://orcid.org/0000-0003-0295-2534)
- Jesús María Hernández‐Rivas (ORCID: https://orcid.org/0000-0002-9661-9371)
- Isabel Granada (ORCID: https://orcid.org/0000-0002-4275-0104)
- Cristina Miguel‐García (ORCID: https://orcid.org/0000-0001-7359-7993)
- Ricardo Sánchez (ORCID: https://orcid.org/0000-0002-6383-0381)
- Sandra Santos‐Mínguez (ORCID: https://orcid.org/0000-0003-0729-207X)
- Esperanza Such (ORCID: https://orcid.org/0000-0001-6892-403X)
- Dolors Costa (ORCID: https://orcid.org/0000-0002-8276-3292)
- Rocío Benito (ORCID: https://orcid.org/0000-0001-9781-4198)
- Ángela Villaverde Ramiro (ORCID: https://orcid.org/0000-0002-7337-7218)
- Sı́lvia Beà (ORCID: https://orcid.org/0000-0001-7192-2385)
- María Herrero (ORCID: https://orcid.org/0000-0001-8719-7165)
- Josep‐María Ribera (ORCID: https://orcid.org/0000-0003-1042-6024)
- Alberto Órfão (ORCID: https://orcid.org/0000-0002-0007-7230)
- Jordi Ribera (ORCID: https://orcid.org/0000-0003-4796-6470)
- Sara González (ORCID: https://orcid.org/0000-0003-2710-075X)
- Susana Bárrena
- Adela Cisneros (ORCID: https://orcid.org/0000-0001-7284-3785)
- Gayane Avetisyan
- J. Acosta
- Raquel Fernández-González
- Anna Puiggros
Institutions
- Universitat Autònoma de Barcelona (ES)
- Universidad de Salamanca (ES)
- Hospital General Universitario Gregorio Marañón (ES)
- Josep Carreras Leukaemia Research Institute (ES)
- Hospital Universitario 12 De Octubre (ES)
- Institut Català d'Oncologia (ES)
- Hospital Clínic de Barcelona (ES)
- Parc de Salut (ES)
- Instituto de Investigación Biomédica de Salamanca (ES)
- Municipal Institute for Medical Research (ES)
- Centro de Investigación del Cáncer (ES)
- Fundación Josep Carreras Contra la Leucemia (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)
Publication Details
- Journal
- Blood Advances
- Published
- 2026-08-28
- DOI
- https://doi.org/10.1182/bloodadvances.2026020029
- Primary Topic
- Acute Lymphoblastic Leukemia research
- Type
- article
- Field-Weighted Citation Impact
- 0.00