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Title: | Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA |
Author: | Sánchez, Ricardo Dorado, Sara Ruíz Heredia, Yanira Martín Muñoz, Alejandro Rosa Rosa, Juan Manuel Ribera, Jordi García, Olga Jimenez Ubieto, Ana Carreño Tarragona, Gonzalo Linares, María Rufián, Laura Juárez, Alexandra Carrillo, Jaime Espino, María José Cáceres, Mercedes Expósito, Sara Cuevas, Beatriz Vanegas, Raúl Casado, Luis Felipe Torrent, Anna Zamora, Lurdes Mercadal, Santiago Coll, Rosa Cervera, Marta Morgades, Mireia Hernández Rivas, José Ángel Bravo, Pilar Serí, Cristina Anguita, Eduardo Barragán, Eva Sargas, Claudia Ferrer Marín, Francisca Sánchez Calero, Jorge Sevilla, Julián Ruíz, Elena Villalón, Lucía Herráez, María del Mar Riaza, Rosalía Magro, Elena Steegman, Juan Luis Wang, Chongwu Toledo, Paula de García Gutiérrez, Valentín Ayala, Rosa Ribera, Josep Maria Barrio, Santiago Martínez López, Joaquín |
Keywords: | Leucèmia mieloide Genòmica ADN Myeloid leukemia Genomics DNA |
Issue Date: | 29-Jul-2022 |
Publisher: | Springer Science and Business Media LLC |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41598-022-17271-3 |
It is part of: | Scientific Reports, 2022, vol. 12, num. 13057 |
URI: | http://hdl.handle.net/2445/188760 |
Related resource: | https://doi.org/10.1038/s41598-022-17271-3 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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