RT Journal Article
T1 Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA
A1 Sánchez, Ricardo
A1 Dorado, Sara
A1 Ruíz-Heredia, Yanira
A1 Martín-Muñoz, Alejandro
A1 Rosa-Rosa, Juan Manuel
A1 Ribera, Jordi
A1 García, Olga
A1 Jiménez-Ubieto, Ana
A1 Carreño-Tarragona, Gonzalo
A1 Linares Gómez, María
A1 Rufián, Laura
A1 Juárez, Alexandra
A1 Carrillo, Jaime
A1 Espino, María José
A1 Cáceres, Mercedes
A1 Expósito, Sara
A1 Cuevas, Beatriz
A1 Vanegas, Raúl
A1 Casado, Luis Felipe
A1 Torrent, Anna
A1 Zamora, Lurdes
A1 Mercadal, Santiago
A1 Coll, Rosa
A1 Cervera, Marta
A1 Morgades, Mireia
A1 Hernández-Rivas, José Ángel
A1 Bravo, Pilar
A1 Serí, Cristina
A1 Anguita, Eduardo
A1 Barragán, Eva
A1 Sargas, Claudia
A1 Ferrer-Marín, Francisca
A1 Sánchez-Calero, Jorge
A1 Sevilla, Julián
A1 Ruíz, Elena
A1 Villalón, Lucía
A1 Herráez, María del Mar
A1 Riaza, Rosalía
A1 Magro, Elena
A1 Steegman, Juan Luis
A1 Wang, Chongwu
A1 Toledo, Paula de
A1 García-Gutiérrez, Valentín
A1 Ayala Díaz, Rosa María
A1 Ribera, Josep-Maria
A1 Barrio, Santiago
A1 Martínez López, Joaquín
AB 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 &lt; 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 <jats:italic>BCR::ABL1</jats:italic> &lt; 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.
PB Nature Research
SN 2045-2322
YR 2022
FD 2022-07-29
LK https://hdl.handle.net/20.500.14352/101870
UL https://hdl.handle.net/20.500.14352/101870
LA eng
NO Sánchez R, Dorado S, Ruíz-Heredia Y, Martín-Muñoz A, Rosa-Rosa JM, Ribera J, García O, Jimenez-Ubieto A, Carreño-Tarragona G, Linares M, Rufián L, Juárez A, Carrillo J, Espino MJ, Cáceres M, Expósito S, Cuevas B, Vanegas R, Casado LF, Torrent A, Zamora L, Mercadal S, Coll R, Cervera M, Morgades M, Hernández-Rivas JÁ, Bravo P, Serí C, Anguita E, Barragán E, Sargas C, Ferrer-Marín F, Sánchez-Calero J, Sevilla J, Ruíz E, Villalón L, Del Mar Herráez M, Riaza R, Magro E, Steegman JL, Wang C, De Toledo P, García-Gutiérrez V, Ayala R, Ribera J-M, Barrio S, Martínez-López J. Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA. Sci Rep 2022;12:13057. https://doi.org/10.1038/s41598-022-17271-3.
NO Centro Nacional para la Información Biotecnológica (Estados Unidos)
DS Docta Complutense
RD 16 abr 2025