Antisense BCR-ABL oligomers cause non-specific inhibition of chronic myeloid leukemia cell lines.
We have examined the effects of antisense oligomers (AOs) of various lengths, sequences and chemistry on the proliferation of eight different cell lines, five derived from patients with chronic myelogenous leukemia (CML) and three from other sources. In general, phosphodiester AOs were inactive, presumably due to degradation by nucleases present in fetal calf serum. Both BA2 and B3A2 phosphorothiolate AOs (but not corresponding sense oligomers) significantly inhibited the proliferation of three CML cell lines (BV173, LAMA84, and KYO1), but the effect was independent of the type of breakpoint expressed by each cell line, suggesting that the inhibition was sequence dependent but not sequence specific. The CML cell lines tested showed different sensitivities to inhibition of proliferation by AOs--lines with defective expression of the normal ABL protooncogene (e.g. BV173) were more readily inhibited than lines with a normal ABL message (e.g. K562). We conclude that further studies are necessary to delineate the precise mechanism(s) by which CML cell proliferation is inhibited by AOs.
O'Brien
S G
SG
Department of Haematology, Royal Postgraduate Medical School, London, UK.
Kirkland
M A
MA
Melo
J V
JV
Rao
M H
MH
Davidson
R J
RJ
McDonald
C
C
Goldman
J M
JM
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D016376:Oligonucleotides, Antisense; D016044:Fusion Proteins, bcr-abl