Dao-Yu Zhang1,2, Xiao-Qing Yuan1,2, Han Yan1,2, Shan Cao1,2, Wei Zhang1,2, Xiao-Lin Li3, Hui Zeng3, Xiao-Ping Chen1,2,4. 1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China. 2. Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China. 3. Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha 410008, Hunan, PR China. 4. Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, Hunan, PR China.
Abstract
AIM: DCK is a rate-limiting enzyme in cytarabine activation. rs4643786 and rs67437265 (P122S) variants are reported to affect DCK activity. PATIENTS & METHODS: A total of 282 newly diagnosed acute myeloid leukemia (AML) patients were treated with cytarabine combined chemotherapy and genotyped for rs4643786 and rs67437265. Prognosis data were obtained through regular follow-up. DCK mRNA expression was detected in pretreatment blood or bone marrow mononuclear cells. RESULTS: rs4643786 showed strong linkage disequilibrium with rs67437265. rs4643786 CT heterozygotes showed significantly higher complete remission rate (p = 0.028), superior overall survival (p = 0.006) and relapse-free survival (p = 0.020) than wild-type TT homozygotes. rs4643786 polymorphism was an independent predictor for AML prognosis. CONCLUSION: DCK rs4643786 may serve as an independent predictor of drug response and AML outcome.
AIM: DCK is a rate-limiting enzyme in cytarabine activation. rs4643786 and rs67437265 (P122S) variants are reported to affect DCK activity. PATIENTS & METHODS: A total of 282 newly diagnosed acute myeloid leukemia (AML) patients were treated with cytarabine combined chemotherapy and genotyped for rs4643786 and rs67437265. Prognosis data were obtained through regular follow-up. DCK mRNA expression was detected in pretreatment blood or bone marrow mononuclear cells. RESULTS:rs4643786 showed strong linkage disequilibrium with rs67437265. rs4643786 CT heterozygotes showed significantly higher complete remission rate (p = 0.028), superior overall survival (p = 0.006) and relapse-free survival (p = 0.020) than wild-type TT homozygotes. rs4643786 polymorphism was an independent predictor for AML prognosis. CONCLUSION:DCKrs4643786 may serve as an independent predictor of drug response and AML outcome.
Authors: Abdelrahman H Elsayed; Xueyuan Cao; Amit K Mitra; Huiyun Wu; Susana Raimondi; Christopher Cogle; Zeina Al-Mansour; Raul C Ribeiro; Alan Gamis; Edward Anders Kolb; Richard Aplenc; Todd A Alonzo; Soheil Meshinchi; Jeffrey Rubnitz; Stanley Pounds; Jatinder K Lamba Journal: J Clin Oncol Date: 2022-01-06 Impact factor: 50.717
Authors: Abdelrahman H Elsayed; Xueyuan Cao; Kristine R Crews; Varsha Gandhi; William Plunkett; Jeffrey E Rubnitz; Raul C Ribeiro; Stanley B Pounds; Jatinder K Lamba Journal: Pharmacogenomics Date: 2018-08-08 Impact factor: 2.533