title: Impact of ABC single nucleotide polymorphisms upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia.
abstract: Anthracycline uptake could be affected by efflux pumps of the ABC family. The influence of 7 SNPs of ABC genes was evaluated in 225 adult de novo acute myeloid leukemia (AML) patients. After multivariate logistic regression there were no significant differences in complete remission, though induction death was associated to ABCB1 triple variant haplotype (p = .020). The ABCB1 triple variant haplotype was related to higher nephrotoxicity (p = .016), as well as this haplotype and the variant allele of ABCB1 rs1128503, rs2032582 to hepatotoxicity (p = .001; p = .049; p < .001). Furthermore, the variant allele of ABCC1 rs4148350 was related to severe hepatotoxicity (p = .044), and the variant allele of ABCG2 rs2231142 was associated to greater cardiac (p = .004) and lung toxicities (p = .038). Delayed time to neutropenia recovery was observed with ABCB1 rs2032582 variant (p = .047). This study shows the impact of ABC polymorphisms in AML chemotherapy safety. Further prospective studies with larger population are needed to validate these associations.
authors.affiliation: a Unidad de Farmacogenética, Instituto Investigación Sanataria La Fe and Área del Medicamento, Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.|b Servicio de Farmacia, Área del Medicamento. Hospital Universitario y Politécnico La Fe Avda , Valencia , Spain.
authors.forename: Juan Eduardo
authors.initials: JE
authors.lastname: Megías-Vericat
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.affiliation: a Unidad de Farmacogenética, Instituto Investigación Sanataria La Fe and Área del Medicamento, Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.|d Departamento Farmacología, Facultad de Medicina , Universidad de Valencia. Avda , Valencia , Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Herrero
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Moscardó
authors.affiliation: a Unidad de Farmacogenética, Instituto Investigación Sanataria La Fe and Área del Medicamento, Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.|b Servicio de Farmacia, Área del Medicamento. Hospital Universitario y Politécnico La Fe Avda , Valencia , Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Bosó
authors.affiliation: a Unidad de Farmacogenética, Instituto Investigación Sanataria La Fe and Área del Medicamento, Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.|e Department of Internal Medicine, Faculty of Medicine , Pontificia Universidad Católica de Chile. Avda , Santiago , Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Rojas
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: David
authors.initials: D
authors.lastname: Martínez-Cuadrón
authors.affiliation: f Unidad de Bioestadística, Instituto investigación Sanataria La Fe. Avda , Valencia , Spain.
authors.forename: David
authors.initials: D
authors.lastname: Hervás
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Boluda
authors.affiliation: b Servicio de Farmacia, Área del Medicamento. Hospital Universitario y Politécnico La Fe Avda , Valencia , Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: García-Robles
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Rodríguez-Veiga
authors.affiliation: b Servicio de Farmacia, Área del Medicamento. Hospital Universitario y Politécnico La Fe Avda , Valencia , Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martín-Cerezuela
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: José
authors.initials: J
authors.lastname: Cervera
authors.affiliation: d Departamento Farmacología, Facultad de Medicina , Universidad de Valencia. Avda , Valencia , Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Sendra
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Sanz
authors.affiliation: d Departamento Farmacología, Facultad de Medicina , Universidad de Valencia. Avda , Valencia , Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Miguel
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lorenzo
authors.affiliation: b Servicio de Farmacia, Área del Medicamento. Hospital Universitario y Politécnico La Fe Avda , Valencia , Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Poveda
authors.affiliation: c Servicio de Hematología y Hemoterapia. Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Sanz
authors.affiliation: a Unidad de Farmacogenética, Instituto Investigación Sanataria La Fe and Área del Medicamento, Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.|d Departamento Farmacología, Facultad de Medicina , Universidad de Valencia. Avda , Valencia , Spain.|g Unidad de Farmacología Clínica, Área del Medicamento, Hospital Universitario y Politécnico La Fe. Avda , Valencia , Spain.
authors.forename: Salvador F
authors.initials: SF
authors.lastname: Aliño
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D005260:Female; D005838:Genotype; D006801:Humans; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers
keywords: ABC; SNP; Transporter; acute myeloid leukemia; anthracyclines; efficacy; idarubicin; polymorphism; toxicity