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RESEARCH PRODUCT
Impact ofABCsingle nucleotide polymorphisms upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia
José CerveraJuan Eduardo Megías-vericatAntonio MiguelLuis RojasPau MontesinosSalvador F. AliñoJosé Luis PovedaJaime SanzMaría José HerreroMiguel A. SanzLuis SendraAna García-roblesRebeca Rodríguez-veigaDavid Martínez-cuadrónIgnacio LorenzoMaría Martín-cerezuelaDavid HervásBlanca BoludaVirginia BosóFederico Moscardósubject
Male0301 basic medicineOncologyCancer Researchmedicine.medical_specialtyGenotypePharmacogenomic Variantsmedicine.medical_treatmentSingle-nucleotide polymorphismNeutropeniaBiologyPolymorphism Single Nucleotide03 medical and health sciences0302 clinical medicineInternal medicineAntineoplastic Combined Chemotherapy ProtocolsmedicineHumansIdarubicinProspective cohort studyAllelesAgedRetrospective StudiesAged 80 and overChemotherapyHaplotypeInduction chemotherapyMyeloid leukemiaInduction ChemotherapyHematologyMiddle Agedmedicine.diseaseLeukemia Myeloid AcuteTreatment Outcome030104 developmental biologyAmino Acid SubstitutionOncology030220 oncology & carcinogenesisImmunologyATP-Binding Cassette TransportersFemaleBiomarkersmedicine.drugdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-10-06 | Leukemia & Lymphoma |