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.
Wright
L
L
Haematology Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia.
Wilson
S B
SB
Milliken
S
S
Biggs
J
J
Kearney
P
P
D001483:Base Sequence; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016337:RNA, Catalytic; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl