ARE/SUZ12 dual specifically-regulated adenoviral TK/GCV system for CML blast crisis cells

Background: treatment of blast phase chronic myeloid leukemia (bp-cml) remains a challenge,and the median survival is less than 6 months. because effective treatments are lacking,we studied tight targeting of blast crisis cml cells using adenoviral (ad) vectors expressing a hsv-tk system under dual control of a specific suz12 promoter and an antioxidant response element (are). methods: a potential suz12 promoter fragment was designed with bioinformatics databases and identified with a luciferase assay. next,we cloned the are element of the nqo1 gene and developed ad vectors expressing tk kinase or luciferase under the dual control of a specific suz12 promoter and an are element. an in vitro transfection assay with ad-are/suz12-luc was used to determine promoter activity of are/suz12 regulatory element in blast crisis cml cells. after incubating human bp-cml-derived cells with ad-are/suz12-tk and ganciclovir,western blot,cck8,immunofluorescent assays and annexin v assays were conducted to assess the efficacy of an are/suz12 dual-specific tk/gcv system for bp-cml cell lines. results: here,luciferase data confirmed significantly higher and specificer promoter activity of the are/suz12 composite component in cml blast crisis-derived cell lines (k562,kcl22,and k562/g01) compared to hepg2 cells,and ad-as-tk/gcv system could exhibit enhanced apoptotic effects and decreased cell viability for bp-cml cell lines. additionally,ad-as-tk/gcv system altered expression of cycle-related and apoptosis-related proteins in bp-cml cell lines. conclusions: thus,are/suz12 dual targeting tk/gcv system was effective in killing bp-cml cells. moreover,efficacy and specificity of cml cell eradication were enhanced by synergistic effects of are/suz12 dual-specific regulation. we conclude that suicide gene-targeted therapy might hold promise for bp-cml treatment. © 2015 zu et al.; licensee biomed central.