Dysregulated MAPK signaling pathway in acute myeloid leukemia with RUNX1 mutations

Abstract

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 to 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 for define the differential 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 analysis were applied to the above mentioned genesets and overlapped genes. Alteration and importance of MAPK pathway was 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 cells 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.