Pharmacogenetics of Metabolic Genes of Anthracyclines in Acute Myeloid Leukemia

Current Drug Metabolism
Juan E Megías-VericatPau Montesinos

Abstract

Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes. A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity. Polymorphisms in the main enzymes of anthracyclines metabolism (CBR, AKR, NQO1, NOS3) have been related to lower enzymatic activity and higher cardiotoxicity. Moreover, variant alleles in the genes of carcinogens and chemotherapy neutralizing enzymes (GST, SULT, NADP(H) oxidase) have been associated with ROS generation and drug efficacy, influencing the survival rates and cardiac toxicities. In addition, genetic variability in the transporters of anthracyclines could affect the intake in cells, including influx (SLC28A3, SLC22A12, SLCO1B1) and efflux transporters (ABCB1, ABCC1, ABCC3, ABCG2). The knowledge of the role of pharmacogenetics in...Continue Reading

Citations

May 25, 2018·Expert Review of Hematology·Giuseppe VisaniPier Paolo Piccaluga
Nov 1, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kelly D GetzRichard Aplenc
Sep 2, 2020·Expert Review of Hematology·Juan Eduardo Megías-VericatPau Montesinos
Jan 1, 2020·Clinical Proteomics·Jaimie DufresneJohn G Marshall
Aug 11, 2020·Expert Opinion on Drug Metabolism & Toxicology·Kateryna PetrykeyMaja Krajinovic
May 1, 2021·Journal of Clinical Medicine·Michał BohdanEwa Lewicka
Mar 7, 2021·Pharmacogenetics and Genomics·Juan Eduardo Megías-VericatPau Montesinos

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