UNMODIFIED PHOSPHODIESTER ANTISENSE OLIGODEOXYNUCLEOTIDES TO THE BCR-ABL JUNCTION DO NOT SUPPRESS PHILADELPHIA-POSITIVE CLONOGENIC CELLS

The BCR-ABL fusion gene is directly involved in the pathogenesis of ch ronic myeloid leukemia (CML). Specific inhibition of the BCR-ABL gene expression with antisense oligodeoxynucleotides has been shown to have profound effects on cell growth in vitro. We examined antisense phosp hodiester oligonucleotides (16-mers at a concentration of 60 mu g/ml) spanning the two possible junction sites K28 (b3a2) and L6 (b2a2) in a clonogenic assay. Single colonies from 9 patients with CML and from p atients with normal bone marrow were screened for BCR-ABL expression w ith a new 'single-tube nested PCR' method. There was a marked reductio n in colony number in the CML group and a lesser growth inhibition in the control group. The number and percentage of BCR-ABL-positive colon ies, however, was not reduced in the CML group. This indicates a nonsp ecific growth inhibition only.