Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression Level Is a Potential Predictive Tool For Response To Decitabine In Patients With Myelodysplastic Syndrome

The DNA methylation inhibitor decitabine is approved for the treatment of myelodysplastic syndromes (MDS). But there remains no effective factor to predict response to decitabine before therapy. Expression level of genes related to decitabine metabolism (including human equilibrative nucleoside transporter 1 (hENT1), hENT2, deoxycytidine kinase (dCK) and cytidine deaminase (CDA)) may influence the therapeutic effect of decitabine. In this study, we aimed to investigate whether the expression level of these genes could predict response to decitabine in MDS patients.

We performed Quantitative Real-Time PCR to examine expression of hENT1, hENT2, dCK and CDA prior to therapy in 60 MDS patients initially treated with decitabine. Response to decitabine and overall survival of patients treated with decitabine was analyzed grouped by the genes expression level.

The patients responded to decitabine presented increased mean hENT1 expression levels compared to non-responders (0.8± 0.2 fold vs. 1.6±0.2 fold, p = 0.008). Among the 31 hENT1 high expression patients, 27(87.1%) achieved response, compared to 15/29 (51.7%) in low hENT1 patients (χ²=8.927, p=0.003). 41.9% (13/31) in hENT1 high expression patients and 10.3% (3/29) in low hENT1 patients achieved CR (χ²=7.646, p=0.006). Patients with hENT1 high expression showed longer survival time compared to low hENT1 patients (22 vs. 16 months; p = 0.027). However, the expression level of hENT2, dCK and CDA did not affect response rate and survival in MDS patients treated with decitabine.

hENT1 expression level is a potential predictive tool for response to decitabine in patients with MDS. High expression of hENT1 predicts prolonged survival in MDS patients treated with decitabine.

No relevant conflicts of interest to declare.