Ribozyme-mediated cleavage of the bcr/abl transcript expressed in chronic myeloid leukemia.

The bcr/abl transcript is specifically expressed in the hematopoietic cells of patients with chronic myeloid leukemia (CML). The Haseloff and Gerlach model was used to design a ribozyme targeted to this transcript. When tested against a synthetic substrate covering the translocation sequence, the ribozyme exhibited site specificity and an absolute requirement for divalent metal ions. Cleavage of the normal bcr was also noted but at a reduced efficiency compared to that exhibited for the bcr/abl substrate. Importantly, cleavage of the full-length bcr/abl mRNA was achieved at physiologic temperature, demonstrating effective ribozyme-mediated cleavage.