Gene expression of hENT1, dCK, CDA, dCMPD and topoisomerase IIα as an indicator of chemotherapy response in AML treated with cytarabine and daunorubicin
Received 24 July 2018
Accepted for publication 3 October 2018
Published 9 November 2018 Volume 2018:10 Pages 5573—5589
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Dr Xueqiong Zhu
Bibi Kulsoom,1,2 Tahir Sultan Shamsi,1 Nasir Ali Afsar3
1Center of Excellence in Molecular Medicine, National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan; 2Department of Biochemistry, Jinnah Medical and Dental College, Karachi, Pakistan; 3Department of Pharmacology, Jinnah Medical and Dental College, Karachi, Pakistan
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-IIa). The expression of these markers was studied in relationship with good (persistent remission) and poor therapeutic response (relapse/resistance).
Results: High Topo-IIa expression in peripheral blood was associated with good response (P=0.006). Relapse was higher among low expressors of Topo-IIa in peripheral blood (OR: 26.25). Bone marrow Topo-IIa 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-IIa (P=0.04) or CDA (P=0.03) expression. High bone marrow Topo-IIa expression also had better DFS at 6 months (P=0.04) and at 12 months (P=0.04).
Conclusion: High expression of Topo-IIa 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.
Keywords: topoisomerase IIα, hENT1, dCMPD, CDA, dCK, survival, AML, antimetabolites, anthracyclines
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