Karami Neda, Ahmadi Mohammad Hossein, Mohammadi Saeed, Maali Amirhosein, Alizadeh Ahad, Pishkhan Dibazar S Haghayegh, Azad Mehdi
Department of Medicine Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Science, Qazvin, Iran.
Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Cell J. 2022 Apr;24(4):163-169. doi: 10.22074/cellj.2022.7798. Epub 2022 Apr 27.
Aberrant alterations in DNA methylation are known as one of the hallmarks of oncogenesis and play a vital role in the progression of acute myeloid leukemia (AML). is a member of the Phosphoinositide 3-kinases family, acting as a tumor suppressor gene. The aim of this study was the evaluation of the expression level and methylation status of in AML.
In this follow-up study on AML patients admitted to Shariati Hospital, Tehran, Iran, the methylation status of [performed by methylation-specific polymerase chain reaction (PCR)] and its expression level (performed by qRT-PCR) were evaluated in three phases: newly diagnosed, under treatment and complete remission. The correlation of the methylation status of , its expression level, and clinical/paraclinical data was analyzed by SPSS ver.25.
This study on 18 patients and five control individuals showed that the CpG-islands of the SMG1 promoter in newly diagnosed cases is hypomethylated compared to the normal group (P=0.002) The fold change of SMG1 expression levels in new cases is 0.464 ± 0.468, while the fold change of expression levels in under-treatment and in-remission patients is 0.973 ± 1.159 and 0.685 ± 0.885, respectively. In under-treatment patients, white blood cell (WBC) count decreases 114176.36 cell/μl with each unit of increase in fold change of SMG1 (P<0.0001), and Hb unit increases 2.062 g/dl with each unit of increase in fold change (P<0.0001). Also, in the remission phase, the Hb unit increases 1.395 g/dl with each unit increase in fold change (P=0.019).
The robust results of our study suggest that the methylation and expression of have a high impact on the pathogenesis of AML. Also, the methylation and expression of can play a prognostic role in AML.
DNA甲基化异常是肿瘤发生的标志之一,在急性髓系白血病(AML)进展中起重要作用。SMG1是磷脂酰肌醇3激酶家族成员,作为肿瘤抑制基因。本研究旨在评估AML中SMG1的表达水平和甲基化状态。
在对伊朗德黑兰沙里亚蒂医院收治的AML患者进行的这项随访研究中,分三个阶段评估SMG1的甲基化状态[通过甲基化特异性聚合酶链反应(PCR)进行]及其表达水平(通过qRT-PCR进行):新诊断、治疗中及完全缓解期。采用SPSS 25版分析SMG1甲基化状态、其表达水平与临床/副临床数据的相关性。
对18例患者和5例对照个体的研究表明,新诊断病例中SMG1启动子的CpG岛与正常组相比呈低甲基化(P = 0.002)。新病例中SMG1表达水平的倍数变化为0.464±0.468,而治疗中及缓解期患者的表达水平倍数变化分别为0.973±1.159和0.685±0.885。在治疗中患者中,SMG1倍数变化每增加一个单位,白细胞(WBC)计数减少114176.36个细胞/μl(P < 0.0001),血红蛋白单位每增加一个单位倍数变化增加2.062 g/dl(P < 0.0001)。此外,在缓解期,血红蛋白单位每增加一个单位倍数变化增加1.395 g/dl(P = 0.019)。
我们研究的有力结果表明,SMG1的甲基化和表达对AML的发病机制有很大影响。此外,SMG1的甲基化和表达可在AML中发挥预后作用。