title: A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment.
abstract: We have used polysome profiling coupled to microarray analysis to examine the translatome of a panel of peripheral blood (PB) B cells isolated from 34 chronic lymphocytic leukaemia (CLL) patients. We have identified a 'ribosome-related' signature in CLL patients with mRNAs encoding for ribosomal proteins and factors that modify ribosomal RNA, e.g. DKC1 (which encodes dyskerin, a pseudouridine synthase), showing reduced polysomal association and decreased expression of the corresponding proteins. Our data suggest a general impact of dyskerin dysregulation on the translational apparatus in CLL and importantly patients with low dyskerin levels have a significantly shorter period of overall survival following treatment. Thus, translational dysregulation of dyskerin could constitute a mechanism by which the CLL PB B cells acquire an aggressive phenotype and thus have a major role in oncogenesis.
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: T
authors.initials: T
authors.lastname: Sbarrato
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: E
authors.initials: E
authors.lastname: Horvilleur
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: T
authors.initials: T
authors.lastname: Pöyry
authors.affiliation: The Babraham Institute, Babraham, Cambridge, UK.
authors.forename: K
authors.initials: K
authors.lastname: Hill
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: L C
authors.initials: LC
authors.lastname: Chaplin
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: R V
authors.initials: RV
authors.lastname: Spriggs
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: M
authors.initials: M
authors.lastname: Stoneley
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: L
authors.initials: L
authors.lastname: Wilson
authors.affiliation: Department of Cancer Studies, Ernest and Helen Scott Haematology Research Institute, University of Leicester, Lancaster Road, Leicester LE1 7H, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jayne
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, 4 Newark Street, Whitechapel, London E1 2AT, UK.
authors.forename: T
authors.initials: T
authors.lastname: Vulliamy
authors.affiliation: Department of Cancer Studies, Ernest and Helen Scott Haematology Research Institute, University of Leicester, Lancaster Road, Leicester LE1 7H, UK.
authors.forename: D
authors.initials: D
authors.lastname: Beck
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, 4 Newark Street, Whitechapel, London E1 2AT, UK.
authors.forename: I
authors.initials: I
authors.lastname: Dokal
authors.affiliation: Department of Cancer Studies, Ernest and Helen Scott Haematology Research Institute, University of Leicester, Lancaster Road, Leicester LE1 7H, UK.
authors.forename: M J S
authors.initials: MJ
authors.lastname: Dyer
authors.affiliation: Cancer Research UK Centre, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Yeomans
authors.affiliation: Cancer Research UK Centre, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: G
authors.initials: G
authors.lastname: Packham
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bushell
authors.affiliation: Department of Cancer Studies, Ernest and Helen Scott Haematology Research Institute, University of Leicester, Lancaster Road, Leicester LE1 7H, UK.
authors.forename: S D
authors.initials: SD
authors.lastname: Wagner
authors.affiliation: Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Willis
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002466:Cell Nucleolus / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015151:Immunoblotting; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D039642:Eukaryotic Initiation Factors; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins