Association between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients
| Autor: | Natalia Estrada, Lurdes Zamora, Francisca Ferrer-Marín, Laura Palomo, Olga García, Patricia Vélez, Iris De la Fuente, Miguel Sagüés, Marta Cabezón, Montserrat Cortés, Rolando Omar Vallansot, María Alicia Senín-Magán, Concepción Boqué, Blanca Xicoy |
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| Přispěvatelé: | [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. [Cortes M] Hospital General de Granollers, Granollers, Spain, Departament de Salut, Institut Català de la Salut, [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, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Other subheadings::Other subheadings::/antagonists & inhibitors [Other subheadings]
chronic myeloid leukemia imatinib major molecular response single-nucleotide polymorphisms Leucèmia mieloide crònica - Tractament Leucèmia mieloide Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia Myeloid [DISEASES] Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] General Medicine Leucèmia mieloide crònica Organic Chemicals::Amides::Benzamides::Imatinib Mesylate [CHEMICALS AND DRUGS] Other subheadings::Other subheadings::/drug therapy [Other subheadings] Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia Myeloid::Leukemia Myelogenous Chronic BCR-ABL Positive [DISEASES] neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide [ENFERMEDADES] Proteïnes quinases Myeloid leukemia Imatinib compuestos orgánicos::amidas::benzamidas::mesilato de imatinib [COMPUESTOS QUÍMICOS Y DROGAS] enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-tirosina cinasas [COMPUESTOS QUÍMICOS Y DROGAS] Otros calificadores::Otros calificadores::/antagonistas & inhibidores [Otros calificadores] Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases [CHEMICALS AND DRUGS] neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mielogenosa crónica BCR-ABL positiva [ENFERMEDADES] Proteïnes quinases - Inhibidors - Ús terapèutic |
| Zdroj: | Scientia Journal of Clinical Medicine; Volume 11; Issue 20; Pages: 6217 |
| Popis: | Chronic myeloid leukemia; Imatinib; Single-nucleotide polymorphisms Leucèmia mieloide crònica; Imatinib; Polimorfismes d'un sol nucleòtid Leucemia mieloide crónica; Imatinib; Polimorfismos de un sólo nucleótido 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. This work was supported by Novartis Oncology (NF.5.1.2-3d.018/2014) and the Fundación Española de Hematología y Hemoterapia (FEHH-SEHH). |
| Databáze: | OpenAIRE |
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