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Background  Cytarabine arabinoside (Ara-C) has been the core of chemotherapy for adult acute myeloid leukemia (AML). Ara-C undergoes a three-step phosphorylation into the active metabolite Ara-C triphosphosphate (ara-CTP). Several enzymes are involved directly or indirectly in either the formation or detoxification of ara-CTP.    Methods  A total of 12 eQTL (expression Quantitative Trait Loci) single nucleotide polymorphisms (SNPs) or tag SNPs in 7 genes including  CMPK1 ,  NME1 ,  NME2 ,  RRM1 ,  RRM2 ,  SAMHD1  and  E2F1  were genotyped in 361 Chinese non-M3 AML patients by using the Sequenom Massarray system. Association of the SNPs with complete remission (CR) rate after Ara-C based induction therapy, relapse-free survival (RFS) and overall survival (OS) were analyzed.    Results  Three SNPs were observed to be associated increased risk of chemoresistance indicated by CR rate ( NME2  rs3744660,  E2F1  rs3213150, and  RRM2  rs1130609), among which two (rs3744660 and rs1130609) were eQTL. Combined genotypes based on  E2F1  rs3213150 and  RRM2  rs1130609 polymorphisms further increased the risk of non-CR. The  SAMHD1  eQTL polymorphism rs6102991 showed decreased risk of non-CR marginally ( P  = 0.055). Three SNPs ( NME1  rs3760468 and rs2302254, and  NME2  rs3744660) were associated with worse RFS, and the  RRM2  rs1130609 polymorphism was marginally associated with worse RFS ( P  = 0.085) and OS ( P  = 0.080). Three SNPs ( NME1  rs3760468,  NME2  rs3744660, and  RRM1  rs183484) were associated with worse OS in AML patients.    Conclusion  Data from our study demonstrated that SNPs in Ara-C and dNTP metabolic pathway predict chemosensitivity and prognosis of AML patients in China.    Electronic supplementary material  The online version of this article (10.1186/s12967-018-1463-1) contains supplementary material, which is available to authorized users.

journal of translational medicine

Association of genetic polymorphisms in genes involved in Ara-C and dNTP metabolism pathway with chemosensitivity and prognosis of adult acute myeloid leukemia (AML)