Raloxifene inhibits the proliferation of pediatric acute myeloid leukemia by targeting the ANP32B gene and regulating C-MYC expression.

OBJECTIVE

Acute myeloid leukemia (AML) is a severe and life-threatening malignant disease of the hematopoietic system. Our previous research found that ANP32B is regulated by super enhancers in pediatric AML and regulates the progression of AML by modulating histone H3K27ac. Using virtual screening technology, we discovered that Raloxifene may be a small-molecule inhibitor targeting ANP32B.

METHODS

Proliferation and apoptosis analysis were used to evaluate the effect of Raloxifene on AML cells. By establishing a xenograft model in NSG mice, 10.0 mg/kg of Raloxifene or a control solvent was intraperitoneally injected into the mice daily, and the tumor progression was monitored. Additionally, RNA sequencing, qRT‒PCR and WB were used to measure gene expression levels after Raloxifene treatment.

RESULTS

The CCK-8 assay showed the IC50 value of Raloxifene in AML cells. The number and size of colony-forming AML cells treated with Raloxifene significantly decreased, and cell apoptosis increased in a dose-dependent manner. The fluorescence values in NSG mice treated with Raloxifene was significantly lower than control group. RNA sequencing revealed that Raloxifene inhibited the expression of the MYC pathway genes in MV4-11 cells.

CONCLUSION

Raloxifene exhibits anti-AML activity both in vitro and in vivo. By targeting ANP32B, Raloxifene effectively inhibits the proliferation of AML cells, induces cell apoptosis, and reduces the expression of C-MYC. Raloxifene may potentially serve as a candidate drug for the treatment of acute myeloid leukemia.