Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA
Year: 2022
Type: article
Study design: Observational Study
Abstract: The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E-4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E-4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.
Source: Scientific Reports
Authors: Ricardo Sánchez, Sara Dorado, Yanira Ruíz-Heredia, Alejandro Martín-Muñoz, Juan Manuel Rosa-Rosa, Jordi Ribera, Olga García, Ana Jimenez-Ubieto, Gonzalo Carreño-Tarragona, María Linares, Laura Rufián, Alexandra Juárez, Jaime Carrillo, María José Espino, Mercedes Cáceres, Sara Expósito, Beatriz Cuevas, Raúl Vanegas, Luis Felipe Casado, Anna Torrent, Lurdes Zamora, Santiago Mercadal, Rosa Coll, Marta Cervera, Mireia Morgades, José Ángel Hernández-Rivas, Pilar Bravo, Cristina Serí, Eduardo Anguita, Eva Barragán, Claudia Sargas, Francisca Ferrer-Marín, Jorge Sánchez-Calero, Julián Sevilla, Elena Ruíz, Lucía Villalón, María del Mar Herráez, Rosalía Riaza, Elena Magro, Juan Luis Steegman, Chongwu Wang, Paula de Toledo, Valentín García-Gutiérrez, Rosa Ayala, Josep-Maria Ribera, Santiago Barrio, Joaquín Martínez-López
Institutions: Research Institute Hospital 12 de Octubre, Spanish National Cancer Research Centre, Hospital Universitario 12 De Octubre, Universidad Carlos III de Madrid, Universitat Autònoma de Barcelona, Josep Carreras Leukaemia Research Institute, Hospital Universitari Germans Trias i Pujol, Universidad Complutense de Madrid, Consejo Superior de Investigaciones Científicas, Instituto Cajal, Hospital Universitario de Burgos, Hospital General Universitario de Ciudad Real, Hospital Virgen de la Salud, Institut Català d'Oncologia, Duran i Reynals Hospital, Hospital Universitari de Girona Doctor Josep Trueta, Hospital Universitari Joan XXIII de Tarragona, Hospital Universitario Infanta Leonor, Hospital Universitario de Fuenlabrada, Hospital Central de la Defensa Gómez Ulla, Hospital Clínico San Carlos, Hospital Universitari i Politècnic La Fe, Hospital General Universitario Morales Meseguer, Centre for Biomedical Network Research on Rare Diseases, Instituto Murciano de Investigación Biosanitaria, Universidad Católica de Murcia, Hospital Universitario de Móstoles, Hospital Infantil Universitario Niño Jesús, Hospital Universitario del Tajo, Hospital Universitario Fundación Alcorcón, Hospital Universitario Severo Ochoa, Hospital Universitario Príncipe de Asturias, Hospital Universitario de La Princesa, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Centro de Investigación Biomédica en Red de Cáncer, Centro de Investigación Biomédica en Red
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,190
OpenAlex ID: W4288700751