Li Yuan, Wu Shu-lan, Bu Ding-fang, Zhu Yan, Zhu Qiang, Cao Xiang-hong
Department of Hematology, First Hospital of Peking University, Beijing 100034, China.
Zhonghua Nei Ke Za Zhi. 2003 Oct;42(10):688-91.
To explore the relationship between methyltransferases and the pathogenesis of acute leukemia (AL) and the leukemic transformation of myelodysplastic syndromes (MDS).
Semi-quantitative RT-PCR method was used to detect the mRNA expression level of DNMT1, 3A and 3B in bone marrow cells from 75 patients with AL or MDS.
There was no significant difference in mRNA expression level of DNMTs between a low-risk MDS group (n = 21) and a normal group. However, increased expression level of DNMT1, 3A and 3B was found in 47.6%, 47.6% and 42.9% of the patients in the low-risk group, respectively, if the upper limit of 80% of the normal controls was considered as the critical level. In high-risk MDS (n = 13), a more proportion of the cases with increased expression level of DNMTs were found, that was 53.8%, 76.9% and 92.3% respectively, and only expression level of DNMT3B was significantly higher than that in the low-risk MDS group (P < 0.01). In the AL group (n = 41) expression level of all the three subtypes was coordinately higher than that in the MDS group (P < 0.01), companying with a more frequency of 92.7%, 97.6% and 100%. Comparing with the AML group, a significantly increased expression level of DNMT1 (P < 0.01) with the same level of DNMT 3A and 3B was interestingly observed in the ALL group.
It is possible that up-regulated DNMTs contribute to the pathogenesis of AL and the leukemic transformation of MDS, and DNMT3B might be the most important enzyme among the three subtypes.
探讨甲基转移酶与急性白血病（AL）发病机制及骨髓增生异常综合征（MDS）白血病转化之间的关系。
采用半定量逆转录聚合酶链反应（RT-PCR）法检测75例AL或MDS患者骨髓细胞中DNMT1、3A和3B的mRNA表达水平。
低危MDS组（n = 21）与正常组之间DNMTs的mRNA表达水平无显著差异。然而，若将正常对照上限的80%作为临界水平，则低危组中分别有47.6%、47.6%和42.9%的患者DNMT1、3A和3B表达水平升高。在高危MDS组（n = 13）中，发现DNMTs表达水平升高的病例比例更高，分别为53.8%、76.9%和92.3%，且只有DNMT3B的表达水平显著高于低危MDS组（P < 0.01）。在AL组（n = 41）中，所有三种亚型的表达水平均协同高于MDS组（P < 0.01），频率分别为92.7%、97.6%和100%。与急性髓系白血病（AML）组相比，急性淋巴细胞白血病（ALL）组中DNMT1的表达水平显著升高（P < 0.01），而DNMT 3A和3B的表达水平相同，这一现象很有趣。
DNMTs上调可能参与AL的发病机制及MDS的白血病转化，且DNMT3B可能是三种亚型中最重要的酶。
