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

• Main Authors: Juan Eduardo Megías-Vericat (Author), David Martínez-Cuadrón (Author), Antonio Solana-Altabella (Author), José Luis Poveda (Author), Pau Montesinos (Author)
• Format: Book
• Published: MDPI AG, 2022-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 <i>SLC</i> and <i>ABC</i> could produce interindividual differences in clinical outcomes. A systematic review was performed to evaluate the influence of <i>SLC</i> and <i>ABC</i> polymorphisms and their combinations on efficacy and safety in AML cohorts. Anthracycline intake was especially influenced by <i>SLCO1B1</i> polymorphisms, associated with lower hepatic uptake, showing higher survival rates and toxicity in AML studies. The variant alleles of <i>ABCB1</i> were related to anthracycline intracellular accumulation, increasing complete remission, survival and toxicity. Similar findings have been suggested with <i>ABCC1</i> and <i>ABCG2</i> polymorphisms. Polymorphisms of <i>SLC29A1</i>, responsible for cytarabine uptake, demonstrated significant associations with survival and response in Asian populations. Promising results were observed with <i>SLC</i> and <i>ABC</i> 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.

Item Description

10.3390/pharmaceutics14040878
1999-4923