Gene Expression of , , , and Topoisomerase IIα As an Indicator of Chemotherapy Response in AML Treated with Cytarabine and Daunorubicin

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 (), deoxycytidine monophosphate deaminase () and topoisomerase IIα (). The expression of these markers was studied in relationship with good (persistent remission) and poor therapeutic response (relapse/resistance).

Results: High expression in peripheral blood was associated with good response (=0.006). Relapse was higher among low expressors of in peripheral blood (OR: 26.25). Bone marrow expression followed a similar trend but did not reach statistical significance. In contrast, patients with high bone marrow expression had poor response (OR: 3; =0.043). One-year disease-free survival (DFS) was better among those with high bone marrow (=0.04) or (=0.03) expression. High bone marrow expression also had better DFS at 6 months (=0.04) and at 12 months (=0.04).

Conclusion: High expression of in peripheral blood is a favorable indicator of persistent remission, good therapeutic response and DFS. High and low expression in bone marrow is associated with poor therapeutic outcome.