title: Let-7a-3 hypomethylation is associated with favorable/intermediate karyotypes but not with survival in acute myeloid leukemia.
abstract: Aberrant methylation of let-7a-3 promoter has been observed in various malignancies. However, the clinical relevance of let-7a-3 methylation remains poorly known in acute myeloid leukemia (AML). This study was to investigate the let-7a-3 methylation status and to explore its clinical significance in AML. let-7a-3 promoter was significantly hypomethylated in AML patients compared to controls (median 4.51 vs 0.49) (P = 0.0003). Receiver operating characteristic curve (ROC) analysis discriminated all patients or cytogenetically normal patients from controls with an areas under the ROC curve (AUC) of 0.737 or 0.783, respectively (P < 0.001). Patients with favorable/intermediate karyotypes had significantly higher let-7a-3 unmethylation than controls. Patients with DNMT3A mutations had a trend of high level of let-7a-3 unmethylation than did those with wild-type DNMT3A (median 6.76 vs 3.66, P = 0.096). There was no significant difference in overall survival between patients with and without hypomethylated let-7a-3 (median 12 vs 5 months, P = 0.103). No correlation was observed between the level of let-7a-3 expression and let-7a-3 unmethylation in AML samples (R = 0.197, P = 0.150). However, the level of let-7a-3 expression was increased in a dose-dependent manner in THP-1 line treated with 5-aza-dC, while the methylation density of let-7a-3 promoter decreased with 5-aza-dC dose. Our findings suggest that let-7a-3 hypomethylation is associated with favorable and intermediate karyotypes but not a prognostic predictor for AML patients. Let-7a-3 expression may be partially regulated by promoter methylation.
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Zhu
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Yao
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: De-Hong
authors.initials: DH
authors.lastname: Wu
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Wen
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Zhao-Qun
authors.initials: ZQ
authors.lastname: Deng
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China. dwqian@yahoo.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China. linjiangmail@sina.com.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, 212002, Zhenjiang, Jiangsu, People's Republic of China. qianjun0007@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D020298:U937 Cells; D055815:Young Adult
chemical_list: D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: 5-aza-dC; Acute myeloid leukemia; Hypomethylation; Let-7a-3