Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj Napoca, Romania.
Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj Napoca, Romania.
Medicina (Kaunas). 2020 Nov 24;56(12):637. doi: 10.3390/medicina56120637.
Mutational analysis has led to a better understanding of acute myeloid leukemia (AML) biology and to an improvement in clinical management. Some of the most important mutations that affect AML biology are represented by mutations in genes related to methylation, more specifically: , , and . Because it has been shown in numerous studies that mutations in these genes lead to similar expression profiles and phenotypes in AML, we decided to assess if mutations in any of those genes interact with other genes important for AML. We downloaded the clinical data, mutational profile and expression profile from the TCGA LAML dataset via cBioPortal. Data were analyzed using classical statistical methods and functional enrichment analysis software represented by STRING and GOrilla. The first step we took was to assess the 196 AML cases that had a mutational profile available and observe the mutations that overlapped with mutations. We observed that mutations significantly overlap with mutations. Because of this, we decided to further investigate the role of mutations in modulating the level of mRNA and observed that mutant cases presented higher levels of mRNA. Because there were only 16 cases of mutant samples and that mutations in this gene determined a change in mRNA expression, we further observed the correlation between and other mRNAs in subgroups regarding the presence of hypermethylating mutations and . Here, we observed that both and mutations increase the number of genes negatively correlated with and that these genes were significantly linked to myeloid activation. In the current study, we have shown that and mutations increase the number of negative correlations of with other transcripts involved in myeloid differentiation.
突变分析使人们对急性髓细胞白血病(AML)的生物学有了更好的理解,并改善了临床管理。一些最重要的影响 AML 生物学的突变是由与甲基化相关的基因中的突变代表的,更具体地说:、、和。因为在许多研究中已经表明,这些基因中的突变导致 AML 中相似的表达谱和表型,所以我们决定评估这些基因中的突变是否与其他对 AML 重要的基因相互作用。我们通过 cBioPortal 从 TCGA LAML 数据集下载了临床数据、突变谱和表达谱。使用经典统计方法和 STRING 和 GOrilla 等功能富集分析软件对数据进行了分析。我们采取的第一步是评估有突变谱可用的 196 例 AML 病例,并观察与 突变重叠的突变。我们观察到 突变与 突变显著重叠。因此,我们决定进一步研究 突变在调节 mRNA 水平中的作用,并观察到 突变病例中 mRNA 的水平更高。由于只有 16 例 突变样本,并且该基因中的突变决定了 mRNA 表达的变化,我们进一步观察了在存在高甲基化突变和 的亚组中 与其他 mRNAs 之间的相关性。在这里,我们观察到 和 突变都增加了与 负相关的基因数量,这些基因与髓样激活显著相关。在本研究中,我们已经表明 和 突变增加了 与其他参与髓样分化的转录物负相关的数量。