Expression levels of nucleoside transporter hENT1 and dCK enzyme, as prognostic factors in patients with AML treated with cytarabine.

Abstract

6599 Background: Cytarabine has been set as the main drug included in different schemas for the treatment of AML patients. This drug requires inflow to the cell by the nucleoside transporter hENT1 and its activation rate is limited by dCK enzyme. Therefore decreased expression levels of these genes may influence response rate to this drug. Methods: AML patients > 15 years, without previous treatment were included. After informed consent signature, peripheral blood was obtained and DNA was extracted by standard methodology. Amplification of hENT1 and dCK genes was done by RT-PCR. Clinical parameters were registered. All patients received cytarabine + doxorrubicine as induction regimen (7 + 3 schema). Descriptive statistics was used. Uni- and multivariate analysis was done to determine factors influencing on response and overall survival. This protocol was approved by local IRB. Results: From January till December 2011, 22 patients have been included. Median age was 36 years (15-72 y), 52.3 % were male. According with FAB classification, M2 subtype was the most frequent (28.5 %). All patients had an adequate performance status (ECOG 1 & 2 = 34 & 66 %, respectively). Cytogenetic risk was considered as intermediate risk in 38 %, followed by unfavorable in 28 %. Complete response was achieved in 58 %. Higher hENT1 expression levels was the only factor influencing on response and survival by Spearmen correlation analysis. Conclusions: These are preliminary results but are highly suggestive that pharmacogenetic analysis regarding cytarabine inflow may be decisive in AML patients. Our results require to be confirmed with a larger sample, and a longer follow-up.