Bromodomain4 inhibitor JQ1 inhibits the proliferation of Ph positive acute lymphocytic leukemia cells and its mechanism

Objective To observe the effect of bromodomain4 (brd4) inhibitor JQ1 on proliferation inhibition and apoptosis of Ph positive acute lymphocytic leukemia (Ph+ ALL) cells, and to explore the influence on the expression of brd4 and its downstream genes (myc and p53), and the reverse effect on bcr-abl. Methods Different concentrations of JQ1 were used on SUP-B15 cells. The proliferation inhibition rate was detected by MTT, the apoptosis rate was determined by flow cytometry (FCM), and the expressions of bcr-abl mRNA, brd4 mRNA, myc mRNA and p53 mRNA were detected by real-time fluorescent quantitative PCR (RT-PCR). Results Different concentrations of JQ1 inhibited SUP-B15 cells proliferation and induced cell apoptosis. The apoptosis rate was significantly increased compared with that in control group with a time-dose dependent manner. Median inhibitory concentration at 72 h was 1.0 μmol/L. At the same time, JQ1 decreased the transcription levels of bcr-abl mRNA, brd4 mRNA and myc mRNA, and increased the transcription level of p53 mRNA. Conclusions As a brd4 inhibitor, JQ1 can decrease the expression of brd4 to affect the expression of its downstream genes myc and p53, meanwhile, it can change the over expression of bcr-abl to suppress the proliferation of Ph+ ALL cells and induce apoptosis. Key words: JQ1; Bromodomain4; SUP-B15 cells; Acute lymphoblastic leukemia