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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
29 07 2022
Historique:
received: 23 02 2022
accepted: 22 07 2022
entrez: 29 7 2022
pubmed: 30 7 2022
medline: 3 8 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35906470
doi: 10.1038/s41598-022-17271-3
pii: 10.1038/s41598-022-17271-3
pmc: PMC9338264
doi:

Substances chimiques

Protein Kinase Inhibitors 0
DNA 9007-49-2
Fusion Proteins, bcr-abl EC 2.7.10.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

13057

Informations de copyright

© 2022. The Author(s).

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Auteurs

Ricardo Sánchez (R)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain. ricardsanchez.hdoc@gmail.com.
Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain. ricardsanchez.hdoc@gmail.com.
Hematological Malignancies Clinical Research Unit, CNIO, Madrid, Spain. ricardsanchez.hdoc@gmail.com.
Altum Sequencing Co., Madrid, Spain. ricardsanchez.hdoc@gmail.com.

Sara Dorado (S)

Altum Sequencing Co., Madrid, Spain.
Computer Science and Engineering Department, Carlos III University, Madrid, Spain.

Yanira Ruíz-Heredia (Y)

Altum Sequencing Co., Madrid, Spain.

Alejandro Martín-Muñoz (A)

Altum Sequencing Co., Madrid, Spain.

Juan Manuel Rosa-Rosa (JM)

Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
Hematological Malignancies Clinical Research Unit, CNIO, Madrid, Spain.

Jordi Ribera (J)

Hematology Department, ICO-Hospital Germans Trias i Pujol. Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.

Olga García (O)

Hematology Department, ICO-Hospital Germans Trias i Pujol. Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.

Ana Jimenez-Ubieto (A)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain.
Hematological Malignancies Clinical Research Unit, CNIO, Madrid, Spain.

Gonzalo Carreño-Tarragona (G)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain.
Hematological Malignancies Clinical Research Unit, CNIO, Madrid, Spain.

María Linares (M)

Hematological Malignancies Clinical Research Unit, CNIO, Madrid, Spain.
Department of Biochemistry and Molecular Biology, Pharmacy School, Universidad Complutense de Madrid, Madrid, Spain.

Laura Rufián (L)

Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
Altum Sequencing Co., Madrid, Spain.

Alexandra Juárez (A)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain.
Altum Sequencing Co., Madrid, Spain.

Jaime Carrillo (J)

Altum Sequencing Co., Madrid, Spain.

María José Espino (MJ)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain.

Mercedes Cáceres (M)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain.

Sara Expósito (S)

Laboratory of Neurophysiology and Synaptic Plasticity, Instituto Cajal, CSIC, Madrid, Spain.

Beatriz Cuevas (B)

Hospital Universitario de Burgos, Burgos, Spain.

Raúl Vanegas (R)

Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.

Luis Felipe Casado (LF)

Hospital Virgen de la Salud, Toledo, Spain.

Anna Torrent (A)

Hematology Department, ICO-Hospital Germans Trias i Pujol. Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.

Lurdes Zamora (L)

Hematology Department, ICO-Hospital Germans Trias i Pujol. Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.

Santiago Mercadal (S)

Hematology Department, ICO-Hospital Duran i Reynals (Bellvitge), Barcelona, Spain.

Rosa Coll (R)

Hematology Department, ICO-Hospital Dr. Josep Trueta, Girona, Spain.

Marta Cervera (M)

Hematology Department, ICO-Hospital Universitari Joan XXIII, Tarragona, Spain.

Mireia Morgades (M)

Hematology Department, ICO-Hospital Germans Trias i Pujol. Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.

José Ángel Hernández-Rivas (JÁ)

Hospital Universitario Infanta Leonor, Madrid, Spain.

Pilar Bravo (P)

Hospital Universitario de Fuenlabrada, Fuenlabrada (Madrid), Spain.

Cristina Serí (C)

Hospital Central de la Defensa Gómez Ulla, Madrid, Spain.

Eduardo Anguita (E)

Hospital Clínico San Carlos, Department of Medicine, UCM, Madrid, Spain.

Eva Barragán (E)

Hospital Universitario y Politécnico La Fe, Valencia, Spain.

Claudia Sargas (C)

Hospital Universitario y Politécnico La Fe, Valencia, Spain.

Francisca Ferrer-Marín (F)

Hospital Universitario Morales-Meseguer, IMIB-Arrixaca, CIBERER, UCAM, Murcia, Spain.

Jorge Sánchez-Calero (J)

Hospital Universitario de Móstoles, Móstoles (Madrid), Spain.

Julián Sevilla (J)

Hospital Universitario Niño Jesús, Madrid, Spain.

Elena Ruíz (E)

Hospital del Tajo, Aranjuez (Madrid), Spain.

Lucía Villalón (L)

Hospital Universitario Fundación Alcorcón, Alcorcón (Madrid), Spain.

María Del Mar Herráez (M)

Hospital Santa Bárbara, Puertollano, Ciudad Real, Spain.

Rosalía Riaza (R)

Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain.

Elena Magro (E)

Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain.

Juan Luis Steegman (JL)

Hospital Universitario La Princesa, Madrid, Spain.

Chongwu Wang (C)

Hosea Precision Medical Technology Co., Ltd., Weihai, Shangdong, China.

Paula de Toledo (P)

Computer Science and Engineering Department, Carlos III University, Madrid, Spain.

Valentín García-Gutiérrez (V)

Hospital Universitario Ramón y Cajal, Instituto de Investigación IRYCIS, Madrid, Spain.

Rosa Ayala (R)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain.
Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
Hematological Malignancies Clinical Research Unit, CNIO, Madrid, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.

Josep-Maria Ribera (JM)

Hematology Department, ICO-Hospital Germans Trias i Pujol. Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.

Santiago Barrio (S)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain.
Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
Hematological Malignancies Clinical Research Unit, CNIO, Madrid, Spain.
Altum Sequencing Co., Madrid, Spain.

Joaquín Martínez-López (J)

Hematology Department, Hospital UniversitarioHospital Universitario 12 Octubre, Madrid, Spain. jmarti01@med.ucm.es.
Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain. jmarti01@med.ucm.es.
Hematological Malignancies Clinical Research Unit, CNIO, Madrid, Spain. jmarti01@med.ucm.es.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain. jmarti01@med.ucm.es.

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Classifications MeSH