Increased DNA methyltransferase expression in leukaemia

Increased DNA methyltransferase expression in leukaemia
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DOI:
10.1038/sj.leu.2400932
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发表时间:
1998-03-01
期刊:
影响因子:
11.4
通讯作者:
Clark, SJ
Clark, SJ
中科院分区:
医学1区
文献类型:
--
作者:
Melki, JR;Warnecke, P;Clark, SJ

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在许多人类肿瘤中,特别是在肿瘤抑制基因的 CpG 岛中,一直观察到异常的 DNA 甲基化,但这些变化的潜在机制仍不清楚。为了确定白血病中 DNA 甲基转移酶的表达是否增加,我们开发了一种标准化的竞争性 RT-PCR 测定法来测量 DNA 甲基转移酶转录物的水平。通过对 12 名急性白血病患者的骨髓 RNA 样本进行该测定,我们观察到与正常骨髓相比,DNA 甲基转移酶 mRNA 水平平均增加了 4.4 倍。这些结果支持但并未证明 DNA 甲基转移酶活性增加与恶性血液疾病相关并可能构成癌发生的关键步骤的假设。
Aberrant DNA methylation has been observed consistently in many human tumours, in particular in the CpG islands of tumour suppressor genes, but the underlying mechanism of these changes remains unclear. To determine whether DNA methyltransferase expression is increased in leukaemia, we developed a standarised competitive RT-PCR assay to measure the level of DNA methyltransferase transcripts. Using this assay on bone marrow RNA samples from 12 patients with acute leukaemia, we observed a 4.4-fold mean increase in the level of DNA methyltransferase mRNA compared with normal bone marrow. These results support but do not prove the hypothesis that an increase in DNA methyltransferase activity is associated with malignant haematological diseases and may constitute a key step in carcinogenesis.