Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, PR China; Institute of Hematology, Zhejiang University, Hangzhou, PR China; Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Zhejiang, Hangzhou, PR China.
Institute of Hematology, Zhejiang University, Hangzhou, PR China.
EBioMedicine. 2018 Feb;28:90-96. doi: 10.1016/j.ebiom.2018.01.031. Epub 2018 Jan 31.
Ten-Eleven-Translocation 1 (TET1) plays a role in the DNA methylation process and gene activation. Recent reports suggest TET1 acts as an oncogene in leukemia development. However, the clinical relevance and biological insight of TET1 expression in cytogenetically normal acute myeloid leukemia (CN-AML) is unknown. In this study, quantification of TET1 transcript by real-time quantitative PCR in bone marrow blasts was performed in 360 CN-AML patients. As a result, high TET1 expression was more common in M0/M1 morphology and genes of NPM1 mutations, and underrepresented in CEBPA double allele mutations in our AML patients. In addition, we found overexpression of TET1 was associated with an inferior overall survival and event free survival in the two independent cohorts. Notably, mRNA and miRNA integrative analyses showed aberrant expression of several hub oncogenes appear to be regulated by some miRNAs like miR-127-5p, miR-494, miR-21 and miR-616 in high TET1 expressers. In conclusion, the TET1 gene expression might serve as a reliable predictor for patients survival in AML.
十十一转移 1（TET1）在 DNA 甲基化过程和基因激活中发挥作用。最近的报告表明，TET1 在白血病的发展中作为癌基因发挥作用。然而，TET1 在细胞遗传学正常的急性髓细胞白血病（CN-AML）中的表达的临床相关性和生物学见解尚不清楚。在这项研究中，通过实时定量 PCR 对 360 例 CN-AML 患者的骨髓母细胞中转录本进行了 TET1 定量。结果表明，在我们的 AML 患者中，高 TET1 表达更常见于 M0/M1 形态和 NPM1 突变基因，而 CEBPA 双等位基因突变则较少。此外，我们发现 TET1 的高表达与两个独立队列中的总生存和无事件生存不良相关。值得注意的是，mRNA 和 miRNA 综合分析表明，几个枢纽癌基因的异常表达似乎受一些 miRNA 如 miR-127-5p、miR-494、miR-21 和 miR-616 的调节，这些 miRNA 在高 TET1 表达者中。总之，TET1 基因表达可能是 AML 患者生存的可靠预测指标。
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