title: Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric acute lymphoblastic leukemia.
abstract: Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Elixabet
authors.initials: E
authors.lastname: López-López
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Gutiérrez-Camino
authors.affiliation: Service of Hematology and Hemotherapy, University Hospital Cruces, Bilbao, Spain.
authors.forename: Maria Ángeles
authors.initials: MÁ
authors.lastname: Piñán
authors.affiliation: Service of Pediatric Oncology and Hematology, University Hospital Vall d' Hebron, VHIR, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Toledo
authors.affiliation: Unit of Pediatric Oncohematology, University Hospital Donostia, San Sebastian, Spain.
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Uriz
authors.affiliation: Department of Neurosciences, Faculty of Medicine and Odontology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ballesteros
authors.affiliation: Service of Pediatric Oncohematology, University Hospital La Paz, Madrid, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: García-Miguel
authors.affiliation: Unit of Pediatric Hematology/Oncology, University Hospital Cruces, Bilbao, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Navajas
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: África
authors.initials: Á
authors.lastname: García-Orad
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics
chemical_list: D035683:MicroRNAs