Impact of ABC single nucleotide polymorphisms upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia

Abstract

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.

Keywords:

• Transporter
• polymorphism
• ABC
• acute myeloid leukemia
• efficacy
• toxicity
• anthracyclines
• idarubicin
• SNP

Acknowledgements

This study was supported by grants from the “Instituto Carlos III” (PIE13/00046) and the “Instituto Investigación Sanatoria La Fe” (2013/0331) assigned to the Pharmacy and Hematology Departments and the Pharmacogenetics Unit of the “Instituto Investigación Sanatoria La Fe” and the “Área del Medicamento” of the “Hospital Universitari i Politècnic La Fe”, Valencia, Spain. Besides, in part this work was supported by the Cooperative Research Thematic Network (RTICC), Grant RD12/0036/014 (ISCIII & ERDF). The study was performed on behalf of the PETHEMA cooperative group and IIS La Fe. Samples have been managed by the La Fe Biobank, licensed as required by Spanish Royal Decree 1716/2011 of 18 November (Ref.: PT13/0010/0026).

We are grateful to Dr. E. Busó from SCSIE (Universidad de Valencia) for his work and help with Mass Array Sequenom^® genotyping.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1231405.