A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment.

Autor: Sbarrato T; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK., Horvilleur E; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK., Pöyry T; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK., Hill K; The Babraham Institute, Babraham, Cambridge, UK., Chaplin LC; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK., Spriggs RV; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK., Stoneley M; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK., Wilson L; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK., Jayne S; Department of Cancer Studies, Ernest and Helen Scott Haematology Research Institute, University of Leicester, Lancaster Road, Leicester LE1 7H, UK., Vulliamy T; 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., Beck D; Department of Cancer Studies, Ernest and Helen Scott Haematology Research Institute, University of Leicester, Lancaster Road, Leicester LE1 7H, UK., Dokal I; 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., Dyer MJ; Department of Cancer Studies, Ernest and Helen Scott Haematology Research Institute, University of Leicester, Lancaster Road, Leicester LE1 7H, UK., Yeomans AM; Cancer Research UK Centre, Faculty of Medicine, University of Southampton, Southampton, UK., Packham G; Cancer Research UK Centre, Faculty of Medicine, University of Southampton, Southampton, UK., Bushell M; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK., Wagner SD; Department of Cancer Studies, Ernest and Helen Scott Haematology Research Institute, University of Leicester, Lancaster Road, Leicester LE1 7H, UK., Willis AE; Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2016 Jun 02; Vol. 7 (6), pp. e2249. Date of Electronic Publication: 2016 Jun 02.
DOI: 10.1038/cddis.2016.148
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: