Manola Kalliopi N, Zachaki Sophia, Kakosaiou Katerina, Ioannidou Agapi, Kalomoiraki Marina, Rampias Theodoros
Laboratory of Health Physics, Radiobiology & Cytogenetics, National Center for Scientific Research (NCSR) "Demokritos", 15341 Athens, Greece.
Biomedical Research Foundation Academy of Athens, 11527 Athens, Greece.
Life (Basel). 2024 Oct 16;14(10):1311. doi: 10.3390/life14101311.
Aberrant gene promoter methylation is one of the hallmarks of Acute Myeloid Leukemia (AML). is an important gene, implicated in sister chromatids cohesion, DNA repair, the regulation of gene transcription, apoptosis and hematopoiesis.
In this study, we investigate the possible implication of promoter methylation in AML pathogenesis using a cohort of AML patients and a cohort of healthy individuals.
promoter methylation was found in 24% of patients and in none of the controls ( = 0.023), indicating a possible contribution to AML development. Interestingly, a statistically higher frequency of methylation was observed in patients with trisomy 8 (9/21, 42.9%, = 0.021), while none of the patients with aberrations of chromosome 11 had gene promoter methylation (0%, 0/11, = 0.048). Patients with monosomal and complex karyotypes showed low frequencies of methylation (7.7% and 15.4%, respectively) without reaching statistical significance. Moreover, mutations were not found to be associated with methylation.
This is the first study which provides evidence for a possible pathogenetic role of promoter methylation in AML development and especially in AML with trisomy 8. Further studies of promoter methylation in large series of different AML genetic subgroups may contribute to the elucidation of AML pathogenesis and to the identification of new epigenetic biomarkers with diagnostic and prognostic value.
异常的基因启动子甲基化是急性髓系白血病（AML）的特征之一。 是一个重要基因，与姐妹染色单体黏连、DNA修复、基因转录调控、细胞凋亡和造血作用有关。
在本研究中，我们使用一组AML患者和一组健康个体，调查 启动子甲基化在AML发病机制中的可能作用。
在24%的患者中发现了 启动子甲基化，而在对照组中未发现（P = 0.023），表明其可能对AML的发生有作用。有趣的是，在8号染色体三体的患者中观察到甲基化频率在统计学上更高（9/21，42.9%，P = 0.021），而11号染色体异常的患者中均未发生 基因启动子甲基化（0%，0/11，P = 0.048）。单体型和复杂核型的患者甲基化频率较低（分别为7.7%和15.4%），未达到统计学意义。此外，未发现 突变与 甲基化相关。
这是第一项为 启动子甲基化在AML发生，尤其是8号染色体三体AML中可能的致病作用提供证据的研究。对大量不同AML基因亚组中 启动子甲基化的进一步研究可能有助于阐明AML发病机制，并有助于识别具有诊断和预后价值的新的表观遗传生物标志物。
