Sbarrato, T., Horvilleur, E., Poyry, 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. (2016) A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment. Cell Death and Disease, 7 (e2249), 1-10. (doi:10.1038/cddis.2016.148). (PMID:27253413)
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.
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