Gene expression of hENT1, dCK, CDA, dCMPD and topoisomerase IIα as an indicator of chemotherapy response in AML treated with cytarabine and daunorubicin

Abstract

Purpose: Acute myeloid leukemia patients are commonly treated with cytarabine (Ara-C) and anthracyclines but the sustained remission rate is not very promising. We explored the role of drug-metabolizing enzymes and transporters in the therapeutic response. Patients and methods: Bone marrow and peripheral blood samples of 90 newly diagnosed acute myeloid leukemia patients treated with standard 3+7 regimen were analyzed through real-time PCR for expression of human equilibrative nucleoside transporter 1, deoxycytidine kinase, cytidine deaminase (CDA), deoxycytidine monophosphate deaminase (dCMPD) and topoisomerase IIα (Topo-IIα). The expression of these markers was studied in relationship with good (persistent remission) and poor therapeutic response (relapse/resistance). Results: High Topo-IIα expression in peripheral blood was associated with good response (P=0.006). Relapse was higher among low expressors of Topo-IIα in peripheral blood (OR: 26.25). Bone marrow Topo-IIα expression followed a similar trend but did not reach statistical significance. In contrast, patients with high bone marrow dCMPD expression had poor response (OR: 3; P=0.043). One-year disease-free survival (DFS) was better among those with high bone marrow Topo-IIα (P=0.04) or CDA (P=0.03) expression. High bone marrow Topo-IIα expression also had better DFS at 6 months (P=0.04) and at 12 months (P=0.04). Conclusion: High expression of Topo-IIα in peripheral blood is a favorable indicator of persistent remission, good therapeutic response and DFS. High dCMPD and low CDA expression in bone marrow is associated with poor therapeutic outcome.