Downloads provided by UsageCountsAssociation between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients
Copyright policy ) Natalia Estrada; Lurdes Zamora; Francisca Ferrer-Marín; Laura Palomo; Olga García; Patricia Vélez; Iris De la Fuente; +7 Authors
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;
Association between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients
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.
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, Leucèmia mieloide, Leucèmia mieloide crònica, CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases, Single-nucleotide polymorphisms, Major molecular response, Article, DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors, chronic myeloid leukemia, CHEMICALS AND DRUGS::Organic Chemicals::Amides::Benzamides::Imatinib Mesylate, single-nucleotide polymorphisms, DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mielogenosa crónica BCR-ABL positiva, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide, major molecular response, COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::amidas::benzamidas::mesilato de imatinib, chronic myeloid leukemia; imatinib; major molecular response; single-nucleotide polymorphisms, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Leucèmia mieloide crònica - Tractament, Chronic myeloid leukemia, Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores, Proteïnes quinases, Myeloid leukemia, imatinib, COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-tirosina cinasas, Imatinib, Proteïnes quinases - Inhibidors - Ús terapèutic
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, Leucèmia mieloide, Leucèmia mieloide crònica, CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases, Single-nucleotide polymorphisms, Major molecular response, Article, DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors, chronic myeloid leukemia, CHEMICALS AND DRUGS::Organic Chemicals::Amides::Benzamides::Imatinib Mesylate, single-nucleotide polymorphisms, DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mielogenosa crónica BCR-ABL positiva, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide, major molecular response, COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::amidas::benzamidas::mesilato de imatinib, chronic myeloid leukemia; imatinib; major molecular response; single-nucleotide polymorphisms, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Leucèmia mieloide crònica - Tractament, Chronic myeloid leukemia, Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores, Proteïnes quinases, Myeloid leukemia, imatinib, COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-tirosina cinasas, Imatinib, Proteïnes quinases - Inhibidors - Ús terapèutic
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).2 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average views 72 downloads 38 - 72views38downloads
selected citations
Citations provided by BIP!
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Citations provided by BIP!popularityPopularity provided by BIP!
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
Popularity provided by BIP!influenceInfluence provided by BIP!
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Influence provided by BIP!impulseImpulse provided by BIP!
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
Impulse provided by BIP!viewsViews provided by UsageCounts
Views provided by UsageCountsdownloadsDownloads provided by UsageCounts
Downloads provided by UsageCounts 2
Average
Average
Average
72
38
Green
gold
