Department of Immunology, Division of Hematology and Transfusion Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Stem cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Biomed Pharmacother. 2018 Jan;97:1493-1500. doi: 10.1016/j.biopha.2017.11.033. Epub 2017 Nov 20.
DNA methylation is a dynamic process influencing gene expression by altering either coding or non-coding loci. Despite advances in treatment of Acute Lymphoblastic Leukemia (ALL); relapse occurs in approximately 20% of patients. Nowadays, epigenetic factors are considered as one of the most effective mechanisms in pathogenesis of malignancies. These factors are reversible elements which can be potentially regarded as therapy targets and disease prognosis. DNA methylation, which primarily serves as transcriptional suppressor, mostly occurs in CpG islands of the gene promoter regions. This was shown as a key epigenetic factor in inactivating various tumor suppressor genes during cancer initiation and progression. We aimed to review methylation status of key genes involved in hematopoietic malignancies such as IKZF1, CDKN2B, TET2, CYP1B1, SALL4, DLC1, DLX family, TP73, PTPN6, and CDKN1C; and their significance in pathogenesis of ALL. The DNA methylation alterations in promoter regions of the genes have been shown to play crucial roles in tumorigenesis. Methylation -based inactivation of these genes has also been reported as associated with prognosis in acute leukemia. In this review, we also addressed the association of gene expression and methylation pattern in ALL patients.
DNA 甲基化是一种通过改变编码或非编码基因座来影响基因表达的动态过程。尽管急性淋巴细胞白血病(ALL)的治疗取得了进展,但仍有约 20%的患者会复发。如今,表观遗传因素被认为是恶性肿瘤发病机制中最有效的机制之一。这些因素是可逆的,因此可以作为潜在的治疗靶点和疾病预后。DNA 甲基化主要作为转录抑制剂,主要发生在基因启动子区域的 CpG 岛上。这是在癌症发生和进展过程中使各种肿瘤抑制基因失活的关键表观遗传因素。我们旨在综述参与血液恶性肿瘤(如 IKZF1、CDKN2B、TET2、CYP1B1、SALL4、DLC1、DLX 家族、TP73、PTPN6 和 CDKN1C)的关键基因的甲基化状态及其在 ALL 发病机制中的意义。研究表明,基因启动子区域的 DNA 甲基化改变在肿瘤发生中起着关键作用。这些基因的甲基化失活也与急性白血病的预后相关。在本综述中,我们还讨论了 ALL 患者中基因表达与甲基化模式的关系。