Department of Hematology and Blood Transfusion, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Isfahan, Iran.
Biomed Res Int. 2024 May 21;2024:9625043. doi: 10.1155/2024/9625043. eCollection 2024.
Epigenetic alterations have been observed in many hematological malignancies, including acute myeloid leukemia (AML). Many of these alterations result from mutations in DNA methyl transferase (DNMT) enzymes, disabling them to methylate target genes in a proper way. In this case-control study, we investigated the association between R882H mutation in gene and gene methylation in patients with AML. 47 AML patients and 6 controls were included in this study. After DNA extraction, amplification refractory mutation system (ARMS)-PCR was used to evaluate R882H mutations in gene. The high-resolution melting (HRM) method was used to determine the methylation changes of the gene promoter. R882H mutation was only found in 10.6% (5 out of 47) of AML patients. The frequency of gene methylation was significantly higher in patients without R882H mutations compared to patients with R882H mutations ( < 0.05). The DNMT3A R882H mutation is typically present in a minority of AML patients. Nevertheless, this mutation is associated with a reduced frequency of methylation in the DDX43 promoter region.
表观遗传改变在许多血液系统恶性肿瘤中都有观察到，包括急性髓系白血病（AML）。这些改变中的许多是由于 DNA 甲基转移酶（DNMT）酶的突变引起的，使其无法以适当的方式甲基化靶基因。在这项病例对照研究中，我们研究了 AML 患者中 基因和 基因甲基化与 R882H 突变之间的关联。本研究纳入了 47 例 AML 患者和 6 例对照。在提取 DNA 后，采用扩增受阻突变系统（ARMS）-PCR 评估 基因中的 R882H 突变。采用高分辨率熔解（HRM）法测定 基因启动子的甲基化变化。仅在 10.6%（47 例中的 5 例）AML 患者中发现 R882H 突变。与存在 R882H 突变的患者相比，无 R882H 突变的患者中 基因甲基化的频率显著更高（<0.05）。DNMT3A R882H 突变通常在少数 AML 患者中存在。然而，这种突变与 DDX43 启动子区域甲基化频率降低有关。
