A Histone Methytransferase Inhibitor, DZNep, Upregulates SAV1Gene Expression In Human Acute Lymphoid Leukemia Cell Line Molt-4

Objective：To detect the expression of SAV1in de novo ALL patients and Peoplewho not suffering from cancer, then to investigate its clinical significance. To explorethe effect of DZNep on the expression of SAV1, the situation of cell proliferation andthe methylation of H3K9at the promoters of SAV1genes with acute lymphoidleukemia cell line Molt-4, and then provide a new direction for the treatment of acutelymphoblastic leukemia.Methods：The expression of SAV1was detected and its clinical significance wasanalysised in clinical samples (de novo ALL patients vs noncancer patient) withquantitative real-time polymerase chain reaction and Western-blot method. TheCCK-8assay methods was used to evaluate the effect on situation of cell proliferationin Molt-4cells after disposal of DZNep; Real-time qPCR and Western blot wereapplied to identify the expression level of SAV1; The methylation status of H3K9atthe promoters of SAV1genes was measured before and after treated with DZNepusing chromatin immunoprecipitation (ChIP) followed by qPCR.Results：1. The expression of SAV1in de novo ALL patients was significantlydecreased.2. DZNep could inhibit the proliferation of Molt-4cells, The expression ofSAV1gene increased after treated with DZNep.3. Treatment with DZNep inhibiteddimethylation and trimethylation of lysine9on histone H3in the cultured humanleukemia Molt-4cells, but the level of monomethylated did not sinificantly change.Conclusion:1. SAV1was significantly decreased in de novo ALL patients.2.DZNep increased the expression of SAV1gene in Molt-4cells, and decreased histoneH3K9dimethylation and trimethylation levels at the promoters of SAV1genes.