BCR-ABL antisense oligodeoxyribonucleotides suppress the growth of leukemic and normal hematopoietic cells by a sequence-specific but nonantisense mechanism.
We have examined the effect of BCR/ABL junctional antisense phosphodiester oligodeoxyribonucleotides (ODNs) on BV173 and other chronic myeloid leukemia (CML) cell lines. Various control ODNs were used to understand the mechanism of the observed antiproliferative effect. Not only the antisense ODNs but also several control ODNs inhibit the proliferation of the leukemic cell lines. All the ODNs that inhibit the cell proliferation share a TAT consensus sequence at their 3' end. A 1-base mismatch within this consensus sequence abolishes the antiproliferative effect. Mismatches of several bases at any other position within the sequence of the active ODNs do not suppress the observed effect. Similar experiments on normal or CML CD34+ cell fraction led to the same observations. We conclude that the antiproliferative effect of the phosphodiester BCR/ABL antisense ODNs cannot be attributed to an antisense mechanism but rather to a nonelucidated effect of a 3' terminal TAT sequence. This effect is not CML specific.
Vaerman
J L
JL
Laboratoire de Biologie Moléculaire Clinique et Unité d'Hématologie, Cliniques St Luc, Université Catholique de Louvain, Bruxelles, Belgium.
Lammineur
C
C
Moureau
P
P
Lewalle
P
P
Deldime
F
F
Blumenfeld
M
M
Martiat
P
P
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D016384:Consensus Sequence; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D006131:Growth Inhibitors; D016376:Oligonucleotides, Antisense; D016044:Fusion Proteins, bcr-abl