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Antisense BCR-ABL oligomers cause non-specific inhibition of chronic myeloid leukemia cell lines

journal contribution
posted on 1994-12-01, 00:00 authored by S G O'Brien, M A Kirkland, J V Melo, M H Rao, R J Davidson, C McDonald, J M Goldman
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.

History

Journal

Leukemia

Volume

8

Issue

12

Pagination

2156 - 2162

Publisher

Williams & Wilkins

Location

Baltimore, Md.

ISSN

0887-6924

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

[1994, Williams & Wilkins]