The Prognostic Value Of The Methylation Status Of The Brd4 Promoter In De Novo B-cell Acute Lymphoblastic Leukemia

Purpose: To quantitatively test the methylation status of the promoter region around the Brd4 transcription start site in de novo B-cell acute lymphoblastic leukemia(B-ALL)patients and to investigate the correlation of the methylation status with prognosis in B-ALL patientsMethods: A total of 120 patients with newly diagnosed B-ALL were enrolled into Wuhan Union Hospital between January 2014 and December 2015,and their bone marrow samples were simultaneously collected.The methylation status of the promoter region around the Brd4 transcription start site(TSS)in B-ALL patients was quantitatively test with bisulfite sequencing and quantitative PCR.The correlation of the methylation status with overall survival(OS),event-free survival(EFS),complete remission(CR)rates and relapse rates in B-ALL patients was statistically analyzed.Results : Among 120 patients tested,BRD4 promoter hypermethylation(methylation rate ? 50%)is more frequently found in 92(76.67%)B-ALL patients(the hypermethylation group),compared with BRD4 promoter hypomethylation(methylation rate < 50%)in 28(23.33%)B-ALL patients(the hypomethylation group).The hypermethylation group is associated with significantly longer OS and EFS tha t the hypomethylation group(P=0.034 and P=0.018,respectively).The CR rates of the hypermethylation and hypomethylation groups were not statistically significant,85.1%(63/74)and 100%(20/20),respectively.Similar results were observed in the relapse rates,6.2%(12/74)and 10.0 %(2/20),respectively.Conclusions: The methylation status of the Brd4 promoter is tightly associated with OS and EFS,but not the CR rates and the relapse rates,in B-ALL patients.The Brd4 promoter hypermethylation is a valuable predictor of poor prognosis for B-ALL patients.