BCL-2 MESSENGER-RNA-TARGETED RIBOZYMES - EFFECTS ON PROGRAMMED CELL-DEATH IN CHRONIC MYELOGENOUS LEUKEMIA-CELL LINES

We used synthetic RNA transcripts to prove the cleavage capability of ribozymes targeted against bcl-2-related RNAs, No cleavage occurred wh en control oligonucliotides were used. To assess the functional role o f the specific ribozymes in chronic myelogenous leukemia (CML) cell li nes we cultured K562, BV173, and Daudi cells for 48 h after lipofectio n with 10 mu M oligonucleotide. An increase in apoptotic cells, depend ent on ribozyme specificity, was shown in BV173 cells.This finding was underlined by the typical morphological changes, but there is no corr elation with regard to the level of bcl-2 protein expressed. Though bc l-2 appears to interfere with cell death in myeloid cells, bcl-2-targe ted ribozymes do not induce programmed cell death (PCD) by reducing bc l-2 protein levels, but rather by a presently unknown mechanism.