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

Sbarrato, T. et al. (2016) A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment. Cell Death and Disease, 7(6), e2249. (doi: 10.1038/cddis.2016.148) (PMID:27253413) (PMCID:PMC5143378)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Sbarrato, T., Horvilleur, E., Pöyry, T., Hill, K., Chaplin, L. C., Spriggs, R. V., Stoneley, M., Wilson, L., Jayne, S., Vulliamy, T., Beck, D., Dokal, I., Dyer, M. J. S., Yeomans, A. M., Packham, G., Bushell, M., Wagner, S. D., and Willis, A. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Death and Disease
• Publisher: Nature Publishing Group
• ISSN: 2041-4889
• ISSN (Online): 2041-4889
• Published Online: 02 June 2016
• Copyright Holders: Copyright © 2016 Macmillan Publishers Limited
• First Published: First published in Cell Death and Disease 7(6): e2249
• Publisher Policy: Reproduced under a Creative Commons License