S100A9,a calcium-binding protein,participates in the inflammatory process and development of various tumors,thus attracting much attention in the field of cancer biology.This study aimed to investigate the regulatory mechanism of S100A9 and its function involvement in APL.We used real-time quantitative PCR to determine whether PML/RARα affects the expression of S100A9 in NB4 and PR9 cells upon ATRA treatment.ChiP-based PCR and dual-luciferase reporter assay system were used to detect how PML/RARα and PU.1 regulate S100A9 promoter activity.CCK-8 assay and flow cytometry were employed to observe the viability and apoptosis of NB4 cells when S100A9 was overexpressed.Results showed that S100A9 was an ATRA-responsive gene,and PML/RARα was necessary for the ATRA-induced expression of S100A9 in APL cells.In addition,PU.1 could bind to the promoter of S100A9,especially when treated with ATRA in NB4 cells,and promote its activity.More importantly,overexpression of S100A9 induced the apoptosis of NB4 cells and inhibited cell growth.Collectively,our data indicated that PML/RARα and PU.1 were necessary for the ATRA-induced expression of S100A9 in APL cells.Furthermore,S100A9 promoted apoptosis in APL cells and affected cell growth.