AI Article Synopsis
- Acute myeloid leukemia (AML) shows a wide range of 5-year disease-free survival rates, from less than 10% to over 70%, depending on patient groups.
- The study investigates how genetic variations in certain drug pathway genes might influence disease-free survival in AML patients undergoing autologous stem cell transplantation.
- A specific SNP in the ABCC3 gene and another in the GSTM1-GSTM5 locus were linked to significantly shorter disease-free survival times, highlighting the potential role of genetics in AML treatment outcomes.
Article Abstract
Acute myeloid leukemia (AML) is a clinically heterogeneous disease, with a 5-year disease-free survival (DFS) ranging from under 10% to over 70% for distinct groups of patients. At our institution, cytarabine, etoposide and busulfan are used in first or second remission patients treated with a two-step approach to autologous stem cell transplantation (ASCT). In this study, we tested the hypothesis that polymorphisms in the pharmacokinetic and pharmacodynamic pathway genes of these drugs are associated with DFS in AML patients. A total of 1659 variants in 42 genes were analyzed for their association with DFS using a Cox-proportional hazards model. One hundred and fifty-four genetically European patients were used for the primary analysis. An intronic single nucleotide polymorphism (SNP) in ABCC3 (rs4148405) was associated with a significantly shorter DFS (hazard ratios (HR)=3.2, P=5.6 × 10(-6)) in our primary cohort. In addition, a SNP in the GSTM1-GSTM5 locus, rs3754446, was significantly associated with a shorter DFS in all patients (HR=1.8, P=0.001 for 154 European ancestry; HR=1.7, P=0.028 for 125 non-European patients). Thus, for the first time, genetic variants in drug pathway genes are shown to be associated with DFS in AML patients treated with chemotherapy-based autologous ASCT.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068832 | PMC |
| http://dx.doi.org/10.1038/jhg.2013.38 | DOI Listing |
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