Abstract: Objective　To investigate the mechanism of interleukin-1 receptor-associated kinase 1 (IRAK1)/tumor necrosis factor receptor associated factor 6 (TRAF6) pathway on the occurrence and development of acute myeloid leukemia (AML). Methods　Fifty-four patients with AML were selected as the research objects (the AML group), another 30 patients with iron deficiency anemia treated in our hospital were used as the control group. Bone marrow monocytes were isolated from all subjects. Human AML cell lines HL-60, KG-1, U937 and human normal monocyte line THP-1 were cultured in vitro. HL-60 cells were divided into the blank group (transfection Lipofectamine 3000 reagent), the negative control (NC) group (transfection empty plasmid) and the IRAK1 short hairpin RNA (IRAK1 shRNA) group (transfection IRAK1 shRNA). The expression levels of IRAK1 mRNA and TRAF6 mRNA in monocytes were detected by real-time fluorescence quantitative PCR. CCK-8 assay was used to detect the proliferation inhibition rate of HL-60 cells. Flow cytometry was used to detect the apoptosis rate. Western blot assay was used to detect the expression levels of β-catenin, CyclinD1, anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), apoptosis protein Bcl-2 related X protein (Bax) and IRAK1/TRAF6 pathway protein. Results　Compared with the control group, the expression levels of IRAK1 mRNA and TRAF6 mRNA were significantly higher in the AML group (P＜0.05). Compared with those in THP-1 cells, the expression levels of IRAK1 mRNA and TRAF6 mRNA were significantly higher in KG-1, U937 and HL-60 cells, and the HL-60 cells were the highest (P＜0.05). Compared with those in the blank group and the NC group, the inhibition rate of cell proliferation, apoptosis rate and Bax protein expression were significantly higher in the IRAK1 shRNA group, and the expression levels of IRAK1 mRNA, TRAF6 mRNA, β-catenin, CyclinD1, Bcl-2, phosphorylation-IRAK1(p-IRAK1)/IRAK1, TRAF6 and nuclear factor-кB(NF-кB) protein expression were significantly lower (P＜0.05). Conclusion　IRAK1/TRAF6 pathway is related to the occurrence and development of AML. The inhibition of IRAK1/TRAF6 pathway can inhibit the proliferation and promote apoptosis of human AML cell line HL-60. IRAK1/TRAF6 pathway may be a potential target for AML treatment.

Key words: interleukin-1 receptor-associated kinases, TNF receptor-associated factor 6, leukemia, myeloid, acute, NF-kappa B, HL-60 cells, cell proliferation, apoptosis