title: Ribozyme-mediated inhibition of bcr-abl gene expression in a Philadelphia chromosome-positive cell line.
abstract: The bcr-abl fusion gene is the molecular counterpart of the Philadelphia chromosome (Ph1) and is directly involved in the pathogenesis of Ph1+ leukemia. Inhibition of bcr-abl gene expression may have profound effects on the cell biology of Ph1+ cells, as recent experiments with antisense oligonucleotides have shown. In this study we have designed and synthesized a unique ribozyme that is directed against bcr-abl mRNA. The ribozyme cleaved bcr-abl mRNA in a cell-free in vitro system. A DNA-RNA hybrid ribozyme was then incorporated into a liposome vector and transfected into EM-2 cells, a cell line derived from a patient with blast crisis of chronic myelogenous leukemia. The ribozyme decreased levels of detectable bcr-abl mRNA in these cells, inhibited expression of the bcr-abl gene product, p210bcr-abl, and inhibited cell growth. This anti-bcr-abl ribozyme may be a useful tool to study the cell biology of Ph1+ leukemia and may ultimately have therapeutic potential in treating patients with Ph1 leukemias.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010-0269.
authors.forename: D S
authors.initials: DS
authors.lastname: Snyder
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: J L
authors.initials: JL
authors.lastname: Wang
authors.forename: J J
authors.initials: JJ
authors.lastname: Rossi
authors.forename: P
authors.initials: P
authors.lastname: Swiderski
authors.forename: B E
authors.initials: BE
authors.lastname: Kaplan
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
mesh_terms: D001483:Base Sequence; D001752:Blast Crisis; D002455:Cell Division; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016337:RNA, Catalytic; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl; D012260:Ribonucleases; D008274:Magnesium