Dysregulated MAPK signaling pathway in acute myeloid leukemia with RUNX1 mutations
Dysregulated MAPK signaling pathway in acute myeloid leukemia with RUNX1 mutations
复制标题
RUNX1 突变的急性髓系白血病中 MAPK 信号通路失调
DOI：
10.1080/17474086.2022.2108015
复制
发表时间：
2022-08-04
影响因子：
2.8
通讯作者：
Cai, Xiongwei
中科院分区：
文献类型：
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作者：
He, Mingmin;Jia, Yongqin;Cai, Xiongwei
背景：急性髓系白血病(AML)是一种具有遗传改变的血液系统恶性肿瘤。RUNX1是一种造血必需的转录因子，在急性髓系白血病中经常发生突变。RUNX1功能缺失突变与AML患者预后不良相关。研究设计和方法：使用TCGA AML、GSE106291、GSE142700和GSE67609数据集。用R包分析差异表达的miRNAs、miRNA靶基因、RUNX1相关基因、RUNX直接调控基因等。用COX回归分析基因表达与总生存期的关系。对上述基因组和重叠基因进行KEGG和GO分析。结果：RUNX1间接或直接调控K562细胞MAPK通路。K562细胞诱导突变的RUNX1细胞MAPK通路发生改变，p38被抑制后对AraC更敏感。结论：RUNX1可调节MAPK通路，为RUNX1突变的AML患者提供潜在的治疗靶点。
Background: Acute myeloid leukemia (AML) is a hematologic malignancy with genetic alterations. RUNX1, which is an essential transcription factor for hematopoiesis, is frequently mutated in AML. Loss-of-function mutation of RUNX1 is correlated with poor prognosis of AML patients. It is urgent to reveal the underlying mechanism.Research design and methods: TCGA AML, GSE106291, GSE142700, and GSE67609 datasets were used. R package was used to define differentially expressed miRNAs, miRNA target genes, RUNX1-related gene, RUNX directly regulating genes, and so on. The relationship of gene expression with overall survival was analyzed by Cox regression. KEGG and GO analyses were applied to the above-mentioned genesets and overlapped genes. Alteration and importance of MAPK pathway were validated in K562 cells by Western blotting and apoptosis assay in vitro.Results: RUNX1 regulated MAPK pathway indirectly and directly. MAPK pathway was altered in K562-cell-induced mutated RUNX1, and these cells were more sensitive to AraC after p38 was inhibited.Conclusions: RUNX1 could modulate MAPK pathway, which may provide a potential therapeutic target for AML patients with RUNX1 mutations.