关键词: 反转录病毒整合位点1基因, 三氧化二砷, 造血转录因子, 急性髓系白血病

Abstract: Objective: To investigate the effect of arsenic trioxide (ATO) on EVI1 gene in regulating hematopoietic transcription factors in vitro. Methods: Acute myeloid leukemia cell line with high EVI1 gene expression-THP-1 cell line was chosen to study the relative mRNA expressions of EVI1 gene and hematopoietic transcription factors GATA1, GATA2, RUNX1, MPO, LMO2, CMYB, PU.1 and SCL by reverse transcription-real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR) in vitro. Healthy adult peripheral blood mononuclear cells were used as controls. THP-1 cell line was then treated with ATO solution with concentrations of 1 μmol/L, 3 μmol/L, 5 μmol/L. Then the relative mRNA expressions of EVI1 gene and the above-mentioned hematopoietic transcription factors were re-determined by RFQ-PCR. Results: The expressions of GATA2 and CMYB increased in THP-1 cell line expressing high EVI1 gene, and the levels of GATA1, RUNX1, MPO, LMO2, PU.1 and SCL decreased in vitro. ATO had the ability to down-regulate EVI1 gene in a dose-dependent and time-dependent manner, and the in turn regulatory effect on other hematopoietic transcription factors was observed. Conclusions: THP-1 cells have an increased expression of GATA2 and then indirectly influencing other transcription factors to promote the proliferation of immature cells and inhibit the differentiation and maturation of myeloid and erythroid cells. ATO could specifically down-regulate the expression of EVI1 gene and decrease the activation of GATA2.

Key words: Ecotropic viral integration site-1, Arsenic trioxide, Hematopoietic transcription factors, Acute myeloid leukemia