急性白血病/骨髓增生异常综合征患者DNA甲基转移酶亚型的表达

目的　探讨DNA甲基转移酶 (DNMTs)亚型与急性白血病 (AL)发病及骨髓增生异常综合征 (MDS)向AL转化的关系。方法　半定量逆转录 (RT) PCR技术测定 75例AL/MDS患者的DNMT1、3A及 3B的mRNA表达水平。结果　低危MDS组 (2 1例 )DNMT各亚型的表达升高与正常对照组平均值无统计学差异 ,但以正常对照组平均值的 80 %单侧上界为界 ,则分别为 4 7 6 %、4 7 6 %和 4 2 9% ,高于正常对照 (P <0 0 1)。高危MDS组 (13例 )分别为 5 3 8%、76 9%和 92 3%高于正常对照 (P <0 0 1) ,其中DNMT 3B表达显著高于低危MDS组 (P <0 0 1) ,而DNMT1和 3A表达与低危组差异无显著性。AL组 (41例 )DNMT1、3A及 3B分别为 92 7%、97 6 %和 10 0 %高于正常对照 (P <0 0 1) ,且三种DNMT亚型表达水平均显著高于MDS组 (P <0 0 1)。急性淋巴细胞白血病组DNMT1表达显著高于急性髓细胞白血病组 (P <0 0 1) ,而二组的DNMT3A ,3B表达无统计学差异。结论　DNMTs表达水平的增高与AL的发病及MDS向AL转化过程密切相关 ,并以DNMT3B的关系最为密切。

The expression of DNA methyltransferase DNMT1, 3A and 3B in acute leukemia and myelodysplastic syndrome

Objective To explore the relationship between methyltransferases and the pathogenesis of acute leukemia(AL) and the leukemic transformation of myelodysplastic syndromes (MDS) Methods 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 Results 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 Conclusions 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