Ribozymes cleave the AML1/MTG8 fusion transcript and inhibit proliferation of leukemic cells with t(8;21).
The AML1/MTG8 fusion gene is thought to have a critical role in the leukemogenesis of AML with t(8;21)(q22;q22). To specifically inhibit the proliferation of leukemic cells having the AML1/MTG8 fusion gene, we constructed two hammerhead ribozymes against AML1/MTG8. Two cleavage sites were targeted as follows: site 1 for ribozyme 1(Rz1), a CUC located 3 bases upstream from the fusion site; site 2 for ribozyme 2(Rz2), an AUC located 3 bases downstream from the fusion site. In a cell-free system, Rz1 and Rz2 specifically cleaved AML1/MTG8 substrate, dependent on the concentration of ribozymes. When these ribozymes were transfected to Kasumi-1 cells, an AML cell line with AML1/MTG8, they were able to inhibit the cell growth. These data suggest that Rz1 and Rz2 may be applied as a new therapeutic agent in the treatment of AML with t(8;21).
D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D002460:Cell Line; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism*; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016337:RNA, Catalytic; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors