DNA methyltransferase 3a (DNMT3a) gene is a frequently dysregulated epigenetic modifier gene involved in the process of carcinogenesis. Also, there is a dichotomous nature of nitric oxide action with the ability to both promote and repress cancers. There is a host of research work delineating the frequency of DNMT3a mutation in acute myeloid leukemia (AML), but little is known about its level of expression in AML patients or its probable relationship to nitrosative stress. This study aims at the assessment DNMT3a gene expression as well as nitric oxide levels in newly diagnosed adult patients with de novo AML. Moreover, it aims at relating these two variables to other disease features and prognostic indicators as well as treatment outcomes. The study included 45 adult de novo AML patients and 10 healthy control subjects. Measurement of DNMT3a messenger ribonucleic acid (mRNA) transcripts was done by real-time quantitative polymerase chain reaction (RQ-PCR) followed by Sanger sequencing to identify the presence or absence of DNMT3a arginine 882 (R882) mutation. This was followed by the assessment of serum nitrite level as a surrogate marker for nitric oxide radical (NO) using colorimetric methods. DNMT3a gene expression, as well as serum nitrite levels, were significantly higher among AML cases in relation to controls before chemotherapy with P values of < 0.001 and 0.035, respectively. Dividing patients into low and high expressors in relation to the hotspot mutation demonstrated no difference between the two groups in terms of demographic, clinical, and laboratory characteristics or treatment outcomes. DNMT3a gene expression is increased among the AML population in relation to normal healthy controls. This may point out the need for the assessment of the influence of this gene expression on methylcytosine content of tumor samples with the subsequent implementation of hypomethylating agents as a line of therapy in cases exhibiting excessive hypermethylation.

中文翻译：

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DNMT3a 基因表达和活性氮种类在新诊断的埃及新发成人急性髓系白血病患者中的预后意义

DNA 甲基转移酶 3a (DNMT3a) 基因是一种经常失调的表观遗传修饰基因，参与致癌过程。此外，一氧化氮作用具有促进和抑制癌症的能力的二分性质。有大量研究工作描述了急性髓系白血病 (AML) 中 DNMT3a 突变的频率，但对其在 AML 患者中的表达水平或其与亚硝化应激的可能关系知之甚少。本研究旨在评估新诊断的 AML 成人患者的 DNMT3a 基因表达以及一氧化氮水平。此外，它旨在将这两个变量与其他疾病特征和预后指标以及治疗结果联系起来。该研究包括 45 名成人新发 AML 患者和 10 名健康对照受试者。DNMT3a 信使核糖核酸 (mRNA) 转录物的测量通过实时定量聚合酶链反应 (RQ-PCR) 和 Sanger 测序进行，以确定 DNMT3a 精氨酸 882 (R882) 突变的存在或不存在。随后使用比色法评估血清亚硝酸盐水平作为一氧化氮自由基 (NO) 的替代标志物。与化疗前对照相比，AML 病例中 DNMT3a 基因表达以及血清亚硝酸盐水平显着更高，P 值分别<0.001 和 0.035。根据热点突变将患者分为低表达和高表达，表明两组在人口统计学、临床和实验室特征或治疗结果方面没有差异。与正常健康对照相比，AML 人群中 DNMT3a 基因表达增加。这可能表明需要评估该基因表达对肿瘤样品中甲基胞嘧啶含量的影响，随后在表现出过度高甲基化的情况下，将低甲基化剂作为一种治疗方法。