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Ribozymes Cleave the AML1/MTG8 Fusion Transcript and Inhibit Proliferation of Leukemic Cells with t (8;21)

1995; Elsevier BV; Volume: 215; Issue: 2 Linguagem: Inglês

10.1006/bbrc.1995.2483

1090-2104

Hiromichi Matsushita, Hiroyuki Kobayashi, Shuji Mori, Masahiro Kizaki, Y. Ikeda,

Advanced biosensing and bioanalysis techniques

The AMLI/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 AMLI/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).