Journal Article Ppublish
PubMed: 42664485 DOI: 10.1182/bloodadvances.2026020029
Comprehensive genetic characterization of adult BCR::ABL1-negative B-ALL by optical genome mapping and targeted NGS.
Blood Adv 10(21):7299-7310
Authors: Josgrey Navas Acosta, Alberto Hernández-Sánchez, Ángela Villaverde-Ramiro, Sandra Santos, Sara González, Irene Rodríguez, Cristina Miguel, Gayane Avetisyan, Adela Cisneros, Anna Puiggros, Dolors Costa, Sílvia Beà, Raquel Fernández-González, Carolina Martínez-Laperche, Jordi Ribera, Susana Barrena, María Herrero, Mireia Morgades, Ricardo Sánchez, Esperanza Such, Blanca Espinet, Isabel Granada, Alberto Orfao, Josep-María Ribera, Rocío Benito, Jesús María Hernández Rivas
Affiliations
- Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
- Department of Hematology, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain.
- Hospital Universitari i Politecnic La Fe, Valencia, Spain.
- Department of Hematology, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain.
- Institut de recerca contra la Leucèmia Josep Carreras, Barcelona, Spain.
- Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, Barcelona, Spain.
- Translational Research on Hematological Neoplasms Group, Cancer Research Program, Hospital del Mar Research Institute, Barcelona, Spain.
- Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
- Hematopathology Section, Pathology Department, Hospital Clínic de Barcelona, Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
- Departament de Fonaments Clinics, Universitat de Barcelona, Barcelona, Spain.
- Department of Hematology, Hospital Universitario Gregorio Marañón, Instituto de Investigaciones Sanitarias Gregorio Marañón, Madrid, Spain.
- Cytometry Service, Universidad de Salamanca, Salamanca, Spain.
- Department of Hematology, Hospital Doce de Octubre, Madrid, Spain.
- Department of Medicine, Universidad de Salamanca, Salamanca, Spain.
Abstract
Adult B-cell precursor acute lymphoblastic leukemia (B-ALL) is genetically heterogeneous, comprising numerous subtypes. Standard methods leave many patients unclassified and the routine implementation of whole-transcriptome sequencing or whole-genome sequencing is limited. We evaluated a combined workflow of optical genome mapping (OGM) and targeted next-generation sequencing (t-NGS) for the genetic characterization of 100 adult patients with BCR::ABL1-negative B-ALL 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 patients with BCR::ABL1-negative B-ALL into 15 distinct subtypes, reducing the proportion of B-other/unclassified cases from 50% to 16%. OGM was useful in identifying BCR::ABL1-like subtype (26% of cases), associated with postinduction minimal/measurable residual disease (MRD) positivity (72% vs 34%; P = .0011), whereas t-NGS contributed to the detection of mutation-defined subtypes (PAX5 P80R and PAX5 altered), correlated with MRD negativity (91% vs 51%; P = .012). OGM and t-NGS identified genetic patterns of certain subtypes, including a higher prevalence of IKZF1plus in patients with BCR::ABL1-like B-ALL (62% vs 12%; P< .001), JAK-STAT mutations only in patients with CRLF2 rearrangements, and a high prevalence of PAX5 biallelic events (92% vs 2%; P< .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.
MeSH
Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Workflow, Genome, Prevalence, Mutation, Hematologic Diseases