Dysregulated MAPK signaling pathway in acute myeloid leukemia with RUNX1 mutations

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. 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. 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. RUNX1 could modulate MAPK pathway, which may provide a potential therapeutic target for AML patients with RUNX1 mutations.