Blood Bank, Preveza General Hospital, Selefkias 2, 48100, Preveza, Greece.
School of Medicine, University of Crete, Heraklion, Greece.
Med Oncol. 2022 Jul 14;39(10):139. doi: 10.1007/s12032-022-01737-5.
DNA methylation has a well-established role in the pathogenesis, prognosis, and response to treatment in all the spectra of hematological malignancies. However, most of the data reported involve average DNA methylation observed in a sample. The emergence of bisulfite sequencing methods such as enhanced reduced representation that permit analyze adjacent CpGs led to exciting findings. Among these are the epialleles shift and the resulting epigenetic heterogeneity observed in leukemias and lymphomas. Epialleles seem to have an influential role as the cause of mutations that characterize leukemias, may stratify groups with different prognosis and response to treatment, and may be redistributed in the genome at different time points of the disease promoting activation of alternate transcriptional networks. Epiallelic shift may be responsible for the intratumor heterogeneity observed within the cells of the same tumor which increases with disease aggressiveness. It may also responsible for the interpatient heterogeneity explaining why blood cancers exhibit different behavior among different patients. Understanding better epiallelic conformation and the consequent chromatin conformational changes and the pathways that may be affected will permit deeper understanding of hematological malignancies pathogenesis and treatment.
DNA 甲基化在所有血液恶性肿瘤的发病机制、预后和治疗反应中都具有明确的作用。然而，大多数报告的数据都涉及样本中观察到的平均 DNA 甲基化。亚硫酸氢盐测序方法的出现，如增强的简化代表性分析，允许分析相邻的 CpG，从而产生了令人兴奋的发现。其中包括在白血病和淋巴瘤中观察到的表观等位基因移位和由此产生的表观遗传异质性。表观等位基因似乎具有作为导致白血病特征性突变的重要作用，可能对具有不同预后和治疗反应的组进行分层，并且可能在疾病的不同时间点在基因组中重新分布，从而激活替代转录网络。表观等位基因的移位可能是导致同一肿瘤细胞内观察到的肿瘤内异质性的原因，这种异质性随着疾病侵袭性的增加而增加。它也可能是导致不同患者之间血液癌症表现出不同行为的原因。更好地理解表观等位基因构象以及随之而来的染色质构象变化和可能受到影响的途径，将有助于深入了解血液恶性肿瘤的发病机制和治疗。
