研究动态
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促进子甲基化可能会改变新发成人急性髓系白血病患者Galectin-3和12表达的平衡。

Promoter methylation might shift the balance of Galectin-3 & 12 expression in de novo adult acute myeloid leukemia patients.

发表日期:2023
作者: Magda Assem, Rady E El-Araby, Ahmed A Al-Karmalawy, Reem Nabil, Mohamed A M Kamal, Amany Belal, Heba I Ghamry, Mohammed A S Abourehab, Mohammed M Ghoneim, Mohammad Y Alshahrani, Asmaa A El Leithy
来源: Frontiers in Genetics

摘要:

急性髓系白血病(AML)是成人中最常见的白血病类型。低亲和力半乳糖聚糖(galectins)是一类结合半乳糖的蛋白质家族,据报道在许多恶性肿瘤中发挥关键作用,包括AML。Galectin-3和-12是哺乳动物galectin家族的成员。为了了解galectin-3和-12启动子甲基化对它们的表达的影响,我们对未接受任何治疗的原发性白血病细胞进行了亚硫酸盐甲基化特异性(MSP)PCR和亚硫酸盐基因组测序(BGS)来进行研究。在这里,我们展示了与启动子甲基化相关的LGALS12基因表达的显著丧失。在甲基化(M)组中发现表达的最低程度,而未甲基化(U)组的表达程度最高,部分甲基化(P)组的表达处于两者之间。这在我们的样本中不适用于galectin-3,除非分析的CpG位点在所研究的片段框架之外。我们还能够确定galectin-12启动子区域中的四个CpG位点(CpG编号1、5、7和8)必须未甲基化,以便诱导表达。据作者所知,这些发现在早期研究中没有得出结论。版权所有©2023 Assem、El-Araby、Al-Karmalawy、Nabil、Kamal、Belal、Ghamry、Abourehab、Ghoneim、Alshahrani 和 El Leithy。
Acute myeloid leukemia (AML) was reported as the most common type of leukemia among adults. Galectins constitute a family of galactose-binding proteins reported to play a critical role in many malignancies including AML. Galectin-3 and -12 are members of the mammalian galectin family. To understand the contribution of galectin-3 and -12 promoter methylation to their expression, we performed bisulfite methylation-specific (MSP)-PCR and bisulfite genomic sequencing (BGS) of primary leukemic cells in patients with de novo AML before receiving any therapy. Here, we show a significant loss of LGALS12 gene expression in association with promoter methylation. The lowest degree of expression was found in the methylated (M) group while the highest degree was in the unmethylated (U) group and the partially methylated (P) group expression lies in between. This was not the case with galectin-3 in our cohort unless the CpG sites analyzed were outside the frame of the studied fragment. We were also able to identify four CpG sites (CpG number 1, 5, 7& 8) in the promoter region of galectin-12; these sites must be unmethylated so that expression can be induced. As far as the authors know, these findings were not previously concluded in earlier studies.Copyright © 2023 Assem, El-Araby, Al-Karmalawy, Nabil, Kamal, Belal, Ghamry, Abourehab, Ghoneim, Alshahrani and El Leithy.