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TET2 (Ten‐Eleven Translocation 2) gene is a member of TET family that can modify DNA through catalyzing the conversion of 5‐methylcytosine (5‐mC) into 5‐hydroxymethylcytosine (5‐hmC). Although TET2 mutation has been disclosed in a variety of hematopoietic malignancies, the prognostic implication of TET2 expression in acute myeloid leukemia (AML) remains largely elusive. In this study, real‐time quantitative PCR was carried out to detect the level of TET2 transcript in 134 de novo AML patients and 35 healthy donors. TET2 mRNA level was significantly down‐regulated in AML patients compared with controls (p = 0.010). Among the French–American–British (FAB) subtypes, the incidence of TET2 under‐expression in M0/M1 subtypes was significantly higher than in the other subtypes M2/M3/M4/M5/M6 (p = 0.017), and also markedly higher than in the other granulocyte subtypes M2/M3 (p = 0.005). TET2 low‐expressed patients showed a significantly higher frequency of NPM1 mutations than TET2 high‐expressed patients. Although there was no significant difference in complete remission rate between two groups (low and high TET2 expression), patients with low TET2 expression had markedly shorter overall survival (OS) in both non‐M3 and cytogenetically normal AML (CN‐AML) (p = 0.016 and 0.044, respectively). Furthermore, multivariate analysis confirmed the prognostic value of TET2 expression on OS among CN‐AML patients (p = 0.049). Importantly, TET2 expression in complete remission (CR) time was significantly higher than newly diagnosis time (p = 0.001), and was returned to lower level when in relapse time (p < 0.001). These findings indicated that down‐regulation of TET2 expression was a common event and acted as a prognostic and predictive biomarker in CN‐AML patients. [ABSTRACT FROM AUTHOR]

Previous study has revealed that H19 expression is required for efficient tumor growth induced by BCR-ABL in chronic myeloid leukemia (CML). Herein, we further determined H19 expression and its clinical implication in patients with CML. H19 expression and methylation were detected by real-time quantitative PCR and real-time quantitative methylation-specific PCR, and then clinical implication of H19 expression was further analyzed. H19 expression was significantly up-regulated in CML patients ( p < 0.001). H19 expression with an area under receiver operating characteristic curve value of 0.824 might serve as a promising biomarker in distinguishing CML patients from controls. The patients with high H19 expression had a tendency of higher white blood cells and BCR-ABL transcript than those with low H19 expression. H19 overexpression occurred with the higher frequency in blast crisis stage (11/11, 100%), lower in accelerated phase (3/5, 60%), and chronic phase (42/62, 66%) stages. Moreover, paired patients during disease progression with increased BCR-ABL transcript also showed a significant upregulation of H19 expression. Meanwhile, H19 expression was decreased in follow-up patients who achieved complete molecular remission after tyrosine kinase inhibitors-based therapy. Epigenetic studies showed that H19 differentially methylated region/imprinting control region (DMR/ICR) was hypomethylated and associated with H19 expression in CML patients. Moreover, demethylation of H19 DMR/ICR reactivated H19 expression in K562 cells. Collectively, H19 overexpression, a frequent event in CML, was associated with higher BCR-ABL transcript involving in disease progression. Moreover, H19 DMR/ICR hypomethylation in CML may be one of the mechanisms mediating H19 overexpression. [ABSTRACT FROM AUTHOR]