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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/188760
Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA
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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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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. Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA. _Scientific Reports_. 2022. Vol. 12, núm. 13057. [consulta: 9 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/188760]