Benetatos Leonidas, Hatzimichael Eleftheria, Dasoula Aggeliki, Dranitsaris George, Tsiara Stavroula, Syrrou Maria, Georgiou Ioannis, Bourantas Konstantinos L
Department of Hematology, University Hospital of Ioannina, Niarchos Avenue, 45500 Ioannina, Greece.
Leuk Res. 2010 Feb;34(2):148-53. doi: 10.1016/j.leukres.2009.06.019.
Methylation is now established as a fundamental regulator of gene transcription. To investigate this in haematologic malignancies, we evaluated the aberrant promoter methylation of two imprinted genes (MEG3 and SNRPN) in 43 MDS and 42 AML patients. MEG3 hypermethylation occurred in 15 MDS patients (34.9%), and in 20 AML patients (47.6%). SNRPN hypermethylation was observed in 15 MDS patients (34.9%), and in 21 AML patients (50%). There were no significant correlations between WHO subtype, WPSS score, karyotype, haemoglobin levels, white blood cell count, platelet count and CpG methylation of any gene. MEG3 hypermethylation was associated with significantly reduced overall survival in individuals with AML (HR=1.98, p=0.04), while SNRPN CpG methylation was not associated with survival (HR=0.94, p=0.87). In addition, no association between survival and aberrant MEG3 (HR=2.15, p=0.072) or SNRPN methylation (HR=1.08, p=0.85) was observed in patients MDS. Our findings suggest that these genes are abnormally methylated in AML and MDS patients, and methylation of MEG3 confers worse overall prognosis. The MEG3 methylation status may serve as a useful biomarker in leukemia.
甲基化现已被确认为基因转录的一种基本调节因子。为了在血液系统恶性肿瘤中对此进行研究，我们评估了43例骨髓增生异常综合征（MDS）患者和42例急性髓系白血病（AML）患者中两个印记基因（MEG3和SNRPN）启动子的异常甲基化情况。15例MDS患者（34.9%）和20例AML患者（47.6%）出现MEG3高甲基化。15例MDS患者（34.9%）和21例AML患者（50%）观察到SNRPN高甲基化。WHO亚型、WPSS评分、核型、血红蛋白水平、白细胞计数、血小板计数与任何基因的CpG甲基化之间均无显著相关性。MEG3高甲基化与AML患者的总生存期显著降低相关（HR=1.98，p=0.04），而SNRPN CpG甲基化与生存期无关（HR=0.94，p=0.87）。此外，在MDS患者中未观察到生存期与MEG3异常甲基化（HR=2.15，p=0.072）或SNRPN甲基化（HR=1.08，p=0.85）之间存在关联。我们的研究结果表明，这些基因在AML和MDS患者中存在异常甲基化，MEG3甲基化预示着更差的总体预后。MEG3甲基化状态可能是白血病中一种有用的生物标志物。
