title: Concentrative nucleoside transporter 3 as a prognostic indicator for favorable outcome of t(8;21)-positive acute myeloid leukemia patients after cytarabine-based chemotherapy.
abstract: Although acute myeloid leukemia (AML) exhibits diverse responses to chemotherapy, patients harboring the t(8;21) translocation are part of a favorable risk group. However, the reason why this subgroup is more responsive to cytarabine-based therapy has not been elucidated. In the present study, we analyzed expression levels of cytarabine metabolism-related genes in patients diagnosed with AML with or without t(8;21) and investigated their correlation with clinical outcomes after cytarabine-based therapy. Among the 8 genes studied, expression of the concentrative nucleoside transporter 3 (CNT3) gene was significantly higher in t(8;21)-positive patients compared to the others in the test population and the validation cohort (P<0.001 in Mann-Whitney U test; P<0.002 in Pearson's correlation analysis). Additionally, in both multivariate and univariate analyses, t(8;21)-positive patients categorized in a higher CNT3 expression tertile had longer disease-free survival [hazard ratio (HR), 0.117; 95% confidence interval (CI), 0.025-0.557; P=0.008] and overall survival (HR, 0.062; 95% CI, 0.007-0.521; P=0.010) compared to t(8;21)-positive patients in a lower CNT3 expression tertile. Notably, these trends did not occur in t(8;21)-negative patients. Our results demonstrate that CNT3 expression is associated with overall favorable outcomes and is predictive of clinical outcomes in AML patients with t(8;21). This suggests that CNT3 expression can be used to optimize treatment strategies for AML patients.
authors.affiliation: Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Song
authors.affiliation: Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Cho
authors.affiliation: Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Nan Young
authors.initials: NY
authors.lastname: Kim
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Tae-Hyang
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Division of Molecular and Life Science and GenoCheck Co., Ltd., Hanyang University, Ansan, Republic of Korea.
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Hwang
authors.affiliation: Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003561:Cytarabine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D026901:Membrane Transport Proteins; C065171:cif nucleoside transporter; D003561:Cytarabine