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Background  Despite the efficacy of decitabine treatment in myelodysplastic syndrome (MDS), no definite predictor of response is known. In this study, we investigated whether the expression levels of human equilibrative nucleoside transporter 1 ( hENT1 ),  hENT2 , deoxycytidine kinase ( DCK ) and cytidine deaminase ( CDA ) genes could predict response to decitabine in MDS.    Methods  We performed quantitative real-time PCR in marrow mononuclear cells to examine the expression of  hENT1 ,  hENT2 ,  DCK , and  CDA  prior to therapy in 98 MDS patients initially treated with decitabine. Response and overall survival of patients treated with decitabine were analyzed according to gene expression levels.  HENT1  knockdown was performed by shRNA in the SKM-1 cell line, and the effect of this on the demethylation ability of decitabine on long interspersed nucleotide element 1 (LINE1) was investigated.    Results  Patients responding to decitabine presented with significantly higher  hENT1  expression levels than non-responders ( p  = 0.004). Overall response, complete response, and cytogenetic complete response rate in patients with high  hENT1  expression (79.4, 41.3, and 43.8 %) were significantly higher than those in patients with low  hENT1  expression (48.6, 20.0, and 5.9 %, respectively) ( p  = 0.004, 0.033, and 0.006, respectively). In higher-risk MDS, patients with high  hENT1  expression showed prolonged survival compared with those with low  hENT1  expression (22.0 vs 14.0 months;  p  = 0.027). However, the expression levels of  hENT2 ,  DCK , and  CDA  did not affect response rate. Knockdown of  hENT1  in SKM-1 cells weakened the demethylation effect on LINE1 induced by decitabine.    Conclusions  High expression of  hENT1  appears to predict a good response to decitabine and a prolonged survival in higher-risk MDS patients treated with decitabine.  HENT1  expression knockdown weakens the demethylation effect of decitabine.    Electronic supplementary material  The online version of this article (doi:10.1186/s12967-016-0817-9) contains supplementary material, which is available to authorized users.

journal of translational medicine

High expression of the human equilibrative nucleoside transporter 1 gene predicts a good response to decitabine in patients with myelodysplastic syndrome