ANTISENSE BCR-ABL OLIGOMERS CAUSE NONSPECIFIC INHIBITION OF CHRONIC MYELOID-LEUKEMIA CELL-LINES

We have examined the effects of antisense oligomers (AOs) of various l engths, sequences and chemistry on the proliferation of eight differen t cell lines, five derived from patients with chronic myelogenous leuk emia (CML) and three from other sources. In general, phosphodiester AO s were inactive, presumably due to degradation by nucleases present in fetal calf serum. Both B2A2 and B3A2 phosphorothioate AOs (but not co rresponding 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, su ggesting that the inhibition was sequence dependent but not sequence s pecific. The CML cell lines tested showed different sensitivities to i nhibition 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 fu rther studies are necessary to delineate the precise mechanism(s) by w hich CML cell proliferation is inhibited by AOs.