Department of Biotechnology, College of Science, University of Baghdad, Baghdad, Iraq.
Tropical-Biological Research Unit, College of Science, University of Baghdad, Baghdad, Iraq.
Gene. 2024 Apr 30;904:148214. doi: 10.1016/j.gene.2024.148214. Epub 2024 Jan 28.
Acute myeloid leukemia (AML) is a malignant hematological disorder in which aberrant cytokine signaling and inflammation play a role in disease initiation and progression. Interleukin-40 (IL-40) is a novel cytokine encoded by the chromosome 17 open reading frame 99 (C17orf99) gene. This cytokine is involved in mediating inflammation but its biological significance in the pathogenesis of AML has not been investigated. In this case-control and observational study, mRNA expression and DNA methylation of the C17orf99 gene were evaluated in the peripheral blood of AML patients. In addition, the polymorphism of two novel intergenic variants of the C17orf99 gene, rs2004339 A/G and rs2310998 G/A, were explored using a real-time polymerase chain reaction assay. The study was conducted on 131 patients with AML and 106 controls and gene expression and DNA methylation were expressed as fold-change (2). Results revealed that mRNA expression of the C17orf99 gene was down-regulated in AML patients, particularly in females, while up-regulated expression was found in patients with hypoalbuminemia. For DNA methylation, it was up-regulated in AML patients, particularly in females, AML M5 subtype, and CD4-negative and CD14-positive peripheral blood cells. The mutant A allele and the corresponding homozygous AA genotype of rs2004339 was significantly associated with an increased risk of AML. The AA genotype was also associated with significantly up-regulated C17orf99 mRNA expression and DNA methylation of compared to the wild-type GG genotype. In conclusions, C17orf99 mRNA expression showed down-regulated levels in the peripheral blood of AML patients, while DNA methylation was up-regulated. The intergenic variant rs2004339 was associated with susceptibility to AML and had an effect on mRNA expression and DNA methylation.
急性髓系白血病 (AML) 是一种恶性血液疾病，其中异常的细胞因子信号和炎症在疾病的发生和进展中起作用。白细胞介素-40 (IL-40) 是由染色体 17 开放阅读框 99 (C17orf99) 基因编码的新型细胞因子。这种细胞因子参与介导炎症，但它在 AML 发病机制中的生物学意义尚未得到研究。在这项病例对照和观察性研究中，评估了 AML 患者外周血中的 C17orf99 基因的 mRNA 表达和 DNA 甲基化。此外，使用实时聚合酶链反应检测了 C17orf99 基因两个新的基因间变体 rs2004339 A/G 和 rs2310998 G/A 的多态性。该研究共纳入 131 例 AML 患者和 106 例对照，基因表达和 DNA 甲基化为倍数变化 (2)。结果显示，AML 患者的 C17orf99 基因 mRNA 表达下调，尤其是女性患者，而低白蛋白血症患者的表达上调。对于 DNA 甲基化，AML 患者中上调，尤其是女性患者、AML M5 亚型和 CD4 阴性、CD14 阳性外周血细胞中。rs2004339 的突变 A 等位基因和相应的纯合 AA 基因型与 AML 风险增加显著相关。与野生型 GG 基因型相比，AA 基因型还与 C17orf99 mRNA 表达和 DNA 甲基化的显著上调相关。总之，AML 患者外周血中 C17orf99 mRNA 表达下调，而 DNA 甲基化上调。基因间变体 rs2004339 与 AML 易感性相关，并对 mRNA 表达和 DNA 甲基化有影响。
