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 chronic 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 phosphodiester oligonucleotides (16-mers at a concentration of 60 micrograms/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 patients with normal bone marrow were screened for BCR-ABL expression with a new 'single-tube nested PCR' method. There was a marked reduction in colony number in the CML group and a lesser growth inhibition in the control group. The number and percentage of BCR-ABL-positive colonies, however, was not reduced in the CML group. This indicates a nonspecific growth inhibition only.
Käbisch
A
A
Department of Hematology and Oncology, Justus Liebig University, Giessen, Germany.
Pérènyi
L
L
Seay
U
U
Lohmeyer
J
J
Pralle
H
H
D001483:Base Sequence; D002999:Clone Cells; D017931:DNA Primers / Q000737:chemistry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl