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Systematic Review of Pharmacogenetics of ABC and SLC Transporter Genes in Acute Myeloid Leukemia

Antineoplastic uptake by blast cells in acute myeloid leukemia (AML) could be influenced by influx and efflux transporters, especially solute carriers (SLCs) and ATP-binding cassette family (ABC) pumps. Genetic variability in SLC and ABC could produce interindividual differences in clinical outcomes...

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Autores principales: Megías-Vericat, Juan Eduardo, Martínez-Cuadrón, David, Solana-Altabella, Antonio, Poveda, José Luis, Montesinos, Pau
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030330/
https://www.ncbi.nlm.nih.gov/pubmed/35456712
http://dx.doi.org/10.3390/pharmaceutics14040878
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author Megías-Vericat, Juan Eduardo
Martínez-Cuadrón, David
Solana-Altabella, Antonio
Poveda, José Luis
Montesinos, Pau
author_facet Megías-Vericat, Juan Eduardo
Martínez-Cuadrón, David
Solana-Altabella, Antonio
Poveda, José Luis
Montesinos, Pau
author_sort Megías-Vericat, Juan Eduardo
collection PubMed
description Antineoplastic uptake by blast cells in acute myeloid leukemia (AML) could be influenced by influx and efflux transporters, especially solute carriers (SLCs) and ATP-binding cassette family (ABC) pumps. Genetic variability in SLC and ABC could produce interindividual differences in clinical outcomes. A systematic review was performed to evaluate the influence of SLC and ABC polymorphisms and their combinations on efficacy and safety in AML cohorts. Anthracycline intake was especially influenced by SLCO1B1 polymorphisms, associated with lower hepatic uptake, showing higher survival rates and toxicity in AML studies. The variant alleles of ABCB1 were related to anthracycline intracellular accumulation, increasing complete remission, survival and toxicity. Similar findings have been suggested with ABCC1 and ABCG2 polymorphisms. Polymorphisms of SLC29A1, responsible for cytarabine uptake, demonstrated significant associations with survival and response in Asian populations. Promising results were observed with SLC and ABC combinations regarding anthracycline toxicities. Knowledge of the role of transporter pharmacogenetics could explain the differences observed in drug disposition in the blast. Further studies including novel targeted therapies should be performed to determine the influence of genetic variability to individualize chemotherapy schemes.
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spelling pubmed-90303302022-04-23 Systematic Review of Pharmacogenetics of ABC and SLC Transporter Genes in Acute Myeloid Leukemia Megías-Vericat, Juan Eduardo Martínez-Cuadrón, David Solana-Altabella, Antonio Poveda, José Luis Montesinos, Pau Pharmaceutics Systematic Review Antineoplastic uptake by blast cells in acute myeloid leukemia (AML) could be influenced by influx and efflux transporters, especially solute carriers (SLCs) and ATP-binding cassette family (ABC) pumps. Genetic variability in SLC and ABC could produce interindividual differences in clinical outcomes. A systematic review was performed to evaluate the influence of SLC and ABC polymorphisms and their combinations on efficacy and safety in AML cohorts. Anthracycline intake was especially influenced by SLCO1B1 polymorphisms, associated with lower hepatic uptake, showing higher survival rates and toxicity in AML studies. The variant alleles of ABCB1 were related to anthracycline intracellular accumulation, increasing complete remission, survival and toxicity. Similar findings have been suggested with ABCC1 and ABCG2 polymorphisms. Polymorphisms of SLC29A1, responsible for cytarabine uptake, demonstrated significant associations with survival and response in Asian populations. Promising results were observed with SLC and ABC combinations regarding anthracycline toxicities. Knowledge of the role of transporter pharmacogenetics could explain the differences observed in drug disposition in the blast. Further studies including novel targeted therapies should be performed to determine the influence of genetic variability to individualize chemotherapy schemes. MDPI 2022-04-17 /pmc/articles/PMC9030330/ /pubmed/35456712 http://dx.doi.org/10.3390/pharmaceutics14040878 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Systematic Review
Megías-Vericat, Juan Eduardo
Martínez-Cuadrón, David
Solana-Altabella, Antonio
Poveda, José Luis
Montesinos, Pau
Systematic Review of Pharmacogenetics of ABC and SLC Transporter Genes in Acute Myeloid Leukemia
title Systematic Review of Pharmacogenetics of ABC and SLC Transporter Genes in Acute Myeloid Leukemia
title_full Systematic Review of Pharmacogenetics of ABC and SLC Transporter Genes in Acute Myeloid Leukemia
title_fullStr Systematic Review of Pharmacogenetics of ABC and SLC Transporter Genes in Acute Myeloid Leukemia
title_full_unstemmed Systematic Review of Pharmacogenetics of ABC and SLC Transporter Genes in Acute Myeloid Leukemia
title_short Systematic Review of Pharmacogenetics of ABC and SLC Transporter Genes in Acute Myeloid Leukemia
title_sort systematic review of pharmacogenetics of abc and slc transporter genes in acute myeloid leukemia
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030330/
https://www.ncbi.nlm.nih.gov/pubmed/35456712
http://dx.doi.org/10.3390/pharmaceutics14040878
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