Pharmacogenomics and the Treatment of Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous malignancy that is primarily treated with combinations of cytarabine and anthracyclines. Although this scheme remains effective in most of the patients, variability of outcomes in patients has been partly related with their genetic variability. Several pharmacogenetic studies have analyzed the impact of polymorphisms in genes encoding transporters, metabolizers or molecular targets of chemotherapy agents. A systematic review on all eligible studies was carried out in order to estimate the effect of polymorphisms of anthracyclines and cytarabine pathways on efficacy and toxicity of AML treatment. Other emerging genes recently studied in AML, such as DNA repair genes, genes potentially related to chemotherapy response or AML prognosis, have also been included.

Keywords::

• acute myeloid leukemia
• anthracyclines
• cytarabine
• effectiveness
• polymorphism
• SNP
• toxicity

Financial & competing interests disclosure

This study was supported by grants from the ‘Instituto Carlos III’ (PIE13/00046) and the ‘Instituto Investigación Sanitaria La Fe’ (2013/0331) assigned to the Pharmacy and Hematology Departments and the Pharmacogenetics Unit of the ‘Instituto Investigación Sanitaria La Fe’, and the ‘Área del Medicamento’ of the ‘Hospital Universitari i Politècnic La Fe’, Valencia, Spain. This work was supported, in part, by the Cooperative Research Thematic Network (RTICC), grant RD12/0036/014 (ISCIII and ERDF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or ­materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported by grants from the ‘Instituto Carlos III’ (PIE13/00046) and the ‘Instituto Investigación Sanitaria La Fe’ (2013/0331) assigned to the Pharmacy and Hematology Departments and the Pharmacogenetics Unit of the ‘Instituto Investigación Sanitaria La Fe’, and the ‘Área del Medicamento’ of the ‘Hospital Universitari i Politècnic La Fe’, Valencia, Spain. This work was supported, in part, by the Cooperative Research Thematic Network (RTICC), grant RD12/0036/014 (ISCIII and ERDF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or ­materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.