SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study.
BACKGROUND
The mechanism behind poor survival of acute myeloid leukemia (AML) patients with 1-barabinofuranosylcytosine (Ara-C) based treatment remains unclear. This study aimed to assess the pharmacogenomic effects of Ara-C metabolic pathway in patients with AML.


METHODS
The genotypes of 19 single nucleotide polymorphisms (SNPs) of DCK, CDA and SLC29A1from 100 AML patients treated with Ara-C were examined. All the SNPs were screened with ligase detection reaction assay. The transcription analysis of genes was examined by quantitative real time polymerase chain reaction. The association between clinical outcome and gene variants was evaluated by Kaplan-Meier method.


RESULTS
Genotypes of rs9394992 and rs324148 for SLC29A1 in remission patients were significantly different from those in relapsed ones. Post-induction overall survival (OS) significantly decreased in patients with the CC genotype of rs324148 compared with CT and TT genotypes (hazard ratio [HR] = 2.997 [95% confidence interval (CI): 1.71-5.27]). As compared with CT and TT genotype, patients with the CC genotype of rs9394992 had longer survival time (HR = 0.25 [95% CI: 0.075-0.81]; HR = 0.43 [95% CI: 0.24-0.78]) and longer disease-free survival (DFS) (HR = 0.52 [95% CI: 0.29-0.93]; HR = 0.15 [95% CI: 0.05-0.47]) as well As compared with CT and TT genotype, patients with the CC genotype of rs324148 had shorter DFS (HR = 3.18 [95% CI: 1.76-5.76]). Additionally, patients with adverse karyotypes had shorter DFS (HR = 0.17 [95% CI: 0.05-0.54]) and OS (HR = 0.18 [95% CI: 0.05-0.68]).


CONCLUSIONS
AML patients with low activity of SLC29A1 genotype have shorter DFS and OS in Ara-C based therapy. Genotypes of rs9394992 and rs324148 may be independent prognostic predictors for the survival of AML patients.
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. aurorawan@126.com.
Haixia
H
Wan
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. linzhujianyi@hotmail.com.
Jianyi
J
Zhu
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. chenfangyuan62@163.com.
Fangyuan
F
Chen
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. xiaofei_78@126.com.
Fei
F
Xiao
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. honghui_huang@163.com.
Honghui
H
Huang
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. hanxf_2007@126.com.
Xiaofeng
X
Han
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. lucyzg25@126.com.
Lu
L
Zhong
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. zhh_lj@hotmail.com.
Hua
H
Zhong
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. x_lan2008@sohu.com.
Lan
L
Xu
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. nibw1979@126.com.
Beiwen
B
Ni
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. jhzhong28@163.com.
Jihua
J
Zhong
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use*; D003561:Cytarabine / Q000378:metabolism / Q000627:therapeutic use*; D018572:Disease-Free Survival; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D003561:Cytarabine