Song Lei, Jiang Wen, Liu Wei, Ji Ju-Hua, Shi Tai-Feng, Zhang Jie, Xia Chun-Qiu
Department of Paediatrics, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Department of Gastroenterology, Nantong Third People's Hospital, Nantong, Jiangsu, China.
Acta Paediatr. 2016 Mar;105(3):e132-41. doi: 10.1111/apa.13284. Epub 2016 Jan 8.
Protein tyrosine phosphatases receptor type D (PTPRD) is a tumour suppressor gene, and its epigenetic silencing is frequently found in glioblastoma. As aberrant deoxyribonucleic acid (DNA) methylation patterning has been shown to play a role in leukaemogenesis, we studied the promoter methylation, expression profiles and molecular functions of PTPRD in paediatric patients with acute myeloid leukaemia (AML).
Bone marrow specimens were obtained from 32 Chinese patients with a mean age of 7.2 years (range 1.1-16.5). PTPRD and methylation status were evaluated by real-time polymerase chain reaction (PCR) and methylation-specific PCR. Western blot and flow cytometry techniques were also used.
PTPRD expression was decreased by promoter region methylation in six AML cells and methylated in 21 (65.6%) of the 32 samples. In addition, PTPRD expression could be induced by the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, functional studies showed that overexpression of PTPRD in AML cells inhibited cell proliferation and clonogenicity as well as inducing apoptosis. However, PTPRD knockdown increased cell proliferation. These effects were associated with downregulation of cyclin D1, c-myc and upregulation of Bax.
The results of this study demonstrated that PTPRD was a potential tumour suppressor gene inactivated by DNA methylation in paediatric AML.
蛋白酪氨酸磷酸酶受体D型（PTPRD）是一种肿瘤抑制基因，其表观遗传沉默在胶质母细胞瘤中经常被发现。由于异常的脱氧核糖核酸（DNA）甲基化模式已被证明在白血病发生中起作用，我们研究了急性髓系白血病（AML）患儿中PTPRD的启动子甲基化、表达谱及分子功能。
从32例中国患者获取骨髓标本，患者平均年龄7.2岁（范围1.1 - 16.5岁）。通过实时聚合酶链反应（PCR）和甲基化特异性PCR评估PTPRD及其甲基化状态。还使用了蛋白质印迹法和流式细胞术技术。
在6个AML细胞中，PTPRD表达因启动子区域甲基化而降低，32个样本中有21个（65.6%）发生甲基化。此外，DNA去甲基化剂5 - 氮杂 - 2'-脱氧胞苷可诱导PTPRD表达。此外，功能研究表明，AML细胞中PTPRD的过表达抑制细胞增殖和克隆形成能力，并诱导细胞凋亡。然而，PTPRD基因敲低会增加细胞增殖。这些效应与细胞周期蛋白D1、c - myc的下调以及Bax的上调有关。
本研究结果表明，PTPRD是小儿AML中因DNA甲基化而失活的潜在肿瘤抑制基因。
