dc.contributor
Institut Català de la Salut
dc.contributor
[Estrada N, Zamora L, García O] Myeloid Neoplasms Group, Josep Carreras Leukaemia Research Institute, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. [Ferrer-Marín F] Hospital General Universitario Morales Meseguer, CIBERER (CB15/00055), IMIB-Pascual Parrilla, UCAM, Murcia, Spain. [Palomo L] MDS Group, Josep Carreras Leukaemia Research Institute, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Vélez P] ICO-Hospital Duran y Reynals, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Estrada, Natalia
dc.contributor.author
Palomo Diaz, Laura
dc.contributor.author
García, Olga
dc.contributor.author
Vélez, Patricia
dc.contributor.author
Ferrer-Marin, Francisca
dc.contributor.author
Zamora, Lurdes
dc.date.accessioned
2025-10-24T09:34:20Z
dc.date.available
2025-10-24T09:34:20Z
dc.date.issued
2022-11-23T13:27:28Z
dc.date.issued
2022-11-23T13:27:28Z
dc.date.issued
2022-10-21
dc.identifier
Estrada N, Zamora L, Ferrer-Marín F, Palomo L, García O, Vélez P, et al. Association between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients. J Clin Med. 2022 Oct 21;11(20):6217.
dc.identifier
https://hdl.handle.net/11351/8529
dc.identifier
10.3390/jcm11206217
dc.identifier
000873100500001
dc.identifier.uri
http://hdl.handle.net/11351/8529
dc.description.abstract
Chronic myeloid leukemia; Imatinib; Single-nucleotide polymorphisms
dc.description.abstract
Leucèmia mieloide crònica; Imatinib; Polimorfismes d'un sol nucleòtid
dc.description.abstract
Leucemia mieloide crónica; Imatinib; Polimorfismos de un sólo nucleótido
dc.description.abstract
Imatinib is the most common first-line tyrosine kinase inhibitor (TKI) used to treat chronic-phase chronic myeloid leukemia (CP-CML). However, only a proportion of patients achieve major molecular response (MMR), so there is a need to find biological factors that aid the selection of the optimal therapeutic strategy (imatinib vs. more potent second-generation TKIs). The aim of this retrospective study was to understand the contribution of germline single-nucleotide variants (gSNVs) in the achievement of MMR with imatinib. In particular, a discovery cohort including 45 CP-CML patients was analyzed through the DMET array, which interrogates 1936 variants in 231 genes related to the absorption, distribution, metabolism and excretion (ADME) process. Variants statistically significant in the discovery cohort were then tested in an extended and independent cohort of 137 CP-CML patients. Finally, a total of 7 gSNVs (ABCG1-rs492338, ABCB11-rs496550, ABCB11-rs497692, CYP2D6-rs1135840, CYP11B1-rs7003319, MAT1A-rs4934027 and SLC22A1-rs628031) and one haplotype in the ABCB11 gene were significantly associated with the achievement of MMR with first-line imatinibtreatment. In conclusion, we identified a genetic signature of response to imatinib in CP-CML patients that could be useful in selecting those patients that may benefit from starting imatinib as first-line therapy, therefore avoiding the toxicity related to second-generation TKIs.
dc.description.abstract
This work was supported by Novartis Oncology (NF.5.1.2-3d.018/2014) and the Fundación Española de Hematología y Hemoterapia (FEHH-SEHH).
dc.format
application/pdf
dc.relation
Journal of Clinical Medicine;11(20)
dc.relation
https://doi.org/10.3390/jcm11206217
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Leucèmia mieloide crònica - Tractament
dc.subject
Proteïnes quinases - Inhibidors - Ús terapèutic
dc.subject
DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases
dc.subject
Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors
dc.subject
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-tirosina cinasas
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores
dc.title
Association between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
