title: Development of a novel treatment for leukemia directed at tumor-associated mRNA splicing.
abstract: This report describes a novel approach to cancer therapy that targets genes that are preferentially alternatively spliced and expressed in leukemia. We developed CD44v6 and CD44v8 splicing constructs fused with GFP or a humanized fragment of Pseudomonas aeruginosa exotoxin A (hPE24). Transfection of K562 leukemia cells with the GFP-linked splicing constructs led to subsequent production of detectable levels of GFP. Transfection of K562 cells with the hPE24-linked splicing constructs led to significant reduction of cell viability and an increase in the induction of apoptosis. Normal human PBMCs were unaffected by following transfection with these constructs.
authors.affiliation: Department of Biological Sciences, Old Dominion University, Norfolk, VA, USA.
authors.forename: Dayle A
authors.initials: DA
authors.lastname: Daines
authors.forename: Jingping
authors.initials: J
authors.lastname: Sun
authors.forename: Olga N
authors.initials: ON
authors.lastname: Uchakina
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McKallip
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D005098:Exotoxins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics*; D020033:Protein Isoforms; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D049452:Green Fluorescent Proteins; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
keywords: Alternative splicing; Apoptosis; CD44 variant; CML