title: Targeting primary human leukaemia cells with RNA interference: Bcr-Abl targeting inhibits myeloid progenitor self-renewal in chronic myeloid leukaemia cells.
abstract: We have investigated functional outcome of challenging primary chronic myeloid leukaemia (CML) cells with Bcr-Abl fusion sequence-directed RNA interference (RNAi). We targeted the Bcr-Abl b3a2 variant, by RNAi, in primary chronic phase CML cells, and detected strikingly reduced proliferation of myeloid precursor cells expressing this variant. Lack of an effect in cells expressing a distinct Bcr-Abl variant confirmed the specificity of the response. Through the functional targeting of an oncogene in primary human tumour cells, we have demonstrated that Bcr-Abl enhances CML progenitor cell amplification, and that RNAi may be suitable for development as a specific anti-leukaemia treatment.
authors.affiliation: Department of Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, UK.
authors.forename: Jane M E
authors.initials: JM
authors.lastname: Withey
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Marley
authors.forename: Jaspal
authors.initials: J
authors.lastname: Kaeda
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Harvey
authors.forename: Mark R
authors.initials: MR
authors.lastname: Crompton
authors.forename: Myrtle Y
authors.initials: MY
authors.lastname: Gordon
mesh_terms: D049109:Cell Proliferation; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
chemical_list: D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D016044:Fusion Proteins, bcr-abl