Acute myeloid leukemia (AML) is often characterized by the presence of specific and recurrent chromosomal abnormalities. Current treatments have greatly increased remission rate, but relapse still occurs. Therefore, novel therapeutic approaches are required. Previously, using a conditional Cbfb-MYH11 knockin mouse model, we showed that Cbfb-MYH11 induces the expression of a cytokine receptor, IL1RL1. Treatment with IL-33, the only known ligand of IL1RL1, promotes leukemia cell survival in vitro. We further found that IL1RL1 cells survive better with chemotherapy than IL1RL1 population. However, the mechanism is not clear. Here, we show that IL-33 treatment decreased drug sensitivity in the human inv(16) AML cell line ME-1. By RT-PCR, we found that IL-33 increased the expression of IL-4 and IL-6 and led to the activation of both p38 MAPK and NF-κB. We also showed that IL-33 decreased apoptosis with increased phosphorylation of p38 MAPK. Moreover, pre-treatment with MAPK inhibitor attenuated the phosphorylation of p38 enhanced by IL-33 and reversed the anti-apoptotic effect by IL-33. Taken together, our findings give news insights into the potential mechanism of the anti-apoptotic effect by IL-33/IL1RL1 axis in AML which will help in future drug development.
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