Inhibition of Promyelocytic Leukemia (PML)/Retinoic Acid Receptor-α and PML Expression in Acute Promyelocytic Leukemia Cells by Anti-PML Peptide Nucleic Acid

摘要: The fusion protein promyelocytic leukemia (PML)/retinoic acid receptor (RAR)alpha is tightly linked to the pathogenesis of acute (APL); hence, it represents a tumor-associated, transformation-related molecule. In this study, three anti-PML adamantyl-conjugated peptide nucleic (PNA) oligomers previously described as in vitro inhibitors PML/RARalpha translation were combined and used block synthesis NB4 cells. Cationic liposomes achieve sufficient delivery PNAs into Upon treatment cells with liposome/PNA mixture, enhanced cellular uptake PNA (approximately 5-fold compared control) was obtained. Concomitantly, substantial reduction (>90%) expression observed when all together. This resulted dramatic effect on number viability culture after 48 h treatment. phenomenon preceded by induction apoptosis that could be 24 No sign granulocytic differentiation These effects also noted other leukemic cell lines express PML but not transcript. results show possible deliver hematopoietic obtain specific gene inhibition, they suggest growth inhibitory can obtained through expression.