Impact of combinations of single-nucleotide polymorphisms of anthracycline transporter genes upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia

6533b7d1fe1ef96bd125cdd1

RESEARCH PRODUCT

Impact of combinations of single-nucleotide polymorphisms of anthracycline transporter genes upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia

José Luis Poveda Evelyn Acuña-cruz Miguel-angel Sanz Salvador F. Aliño Rebeca Rodríguez-veiga María José Herrero Antonio Solana-altabella Isabel Cano David Martínez-cuadrón Juan Eduardo Megías-vericat Octavio Ballesta-lópez Pau Montesinos Blanca Boluda José Cervera

subject

Adult Cancer Research Genotype Anthracycline Single-nucleotide polymorphism Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Mucositis Humans Medicine Idarubicin Anthracyclines Prospective Studies biology Liver-Specific Organic Anion Transporter 1 business.industry Haplotype Induction chemotherapy Myeloid leukemia Induction Chemotherapy Hematology medicine.disease Multidrug Resistance-Associated Protein 2 Leukemia Myeloid Acute Oncology 030220 oncology & carcinogenesis biology.protein Cancer research ATP-Binding Cassette Transporters business SLCO1B1 030215 immunology medicine.drug

description

Anthracycline uptake could be affected by influx and efflux transporters in acute myeloid leukemia (AML). Combinations of single-nucleotide polymorphisms (SNPs) of wild-type genotype of influx transporters (SLC22A16, SLCO1B1) and homozygous variant genotypes of ABC polymorphisms (ABCB1, ABCC1, ABCC2, ABCG2) were evaluated in 225 adult de novo AML patients. No differences in complete remission were reported, but higher induction death was observed with combinations of SLCO1B1 rs4149056 and ABCB1 (triple variant haplotype, rs1128503), previously associated with ABCB1 and SLCO1B1 SNPs. Several combinations of SLCO1B1 and SLC22A16 with ABCB1 SNPs were associated with higher toxicities, including nephrotoxicity and hepatotoxicity, neutropenia, previously related to ABCB1, and a novel correlation with mucositis. Combination of SLC22A16 rs714368 and ABCG2 rs2231142 was related to cardiac toxicity, reproducing previous correlations with ABCG2. This study shows the impact of transporter polymorphisms in AML chemotherapy safety. Further prospective studies with larger populations are needed to validate these associations.

year	journal	country	edition	language
2020-11-02	Leukemia & Lymphoma

https://doi.org/10.1080/10428194.2020.1839650