Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

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-generat...

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Autores: Sánchez, Ricardo|||0000-0002-6383-0381, Dorado, Sara|||0000-0002-4144-0315, Ruíz-Heredia, Yanira|||0000-0002-9895-2100, Martín-Muñoz, Alejandro|||0000-0002-5180-5760, Rosa-Rosa, J.M.|||0000-0003-0806-6453, Ribera Salas, Jordi|||0000-0003-4796-6470, García, Olga, Jimenez-Ubieto, Ana|||0000-0003-0892-8682, Carreño-Tarragona, Gonzalo|||0000-0002-9570-5542, Linares, Maria, Rufián, Laura, Juárez, Alexandra, Carrillo García, Jaime|||0000-0002-2861-3015, Espino, María José, Cáceres, Mercedes, Expósito, Sara, Cuevas, Beatriz|||0000-0001-7555-3361, Vanegas, Raúl, Casado Montero, Luis Felipe|||0000-0002-8171-0674, Torrent Catarineu, Anna|||0000-0002-3727-5716, Zamora, Lurdes|||0000-0003-1713-7110, Mercadal, Santiago|||0000-0003-4741-7885, Coll, Rosa|||0000-0003-0560-1254, Cervera, Marta, Morgades, Mireia|||0000-0003-0295-2534, Hernández Rivas, José Ángel|||0000-0003-4550-757X, Bravo, Pilar, Serí, Cristina, Anguita, Eduardo|||0000-0003-1386-4943, Barragán, Eva, Sargas, Claudia, Ferrer-Marín, Francisco, Sánchez-Calero, Jorge, Sevilla, Julián|||0000-0002-6852-1860, Ruíz, Elena, Villalón, Lucía, Herráez, María del Mar, Riaza, Rosalía, Magro, Elena, Steegman, Juan Luís, Wang, Chongwu, de Toledo, Paula, García Gutiérrez, Valentín|||0000-0003-4752-0815, Ayala, Rosa|||0000-0002-2699-8353, Ribera, Jose-Maria|||0000-0003-1042-6024, Barrio, Santiago, Martínez-López, Joaquín|||0000-0001-7908-0063
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:270562
Acceso en línea:https://ddd.uab.cat/record/270562
https://dx.doi.org/urn:doi:10.1038/s41598-022-17271-3
Access Level:acceso abierto
Palabra clave:DNA
Drug Resistance, Neoplasm
Fusion Proteins, bcr-abl
Genomics
High-Throughput Nucleotide Sequencing
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mutation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Protein Kinase Inhibitors
Descripción
Sumario: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.

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