A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment.
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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.
AuthorsSbarrato, T; Horvilleur, E; Pöyry, T; Hill, K; Chaplin, LC; Spriggs, RV; Stoneley, M; Wilson, L; Jayne, S; Vulliamy, T; Beck, D; Dokal, I; Dyer, MJ; Yeomans, AM; Packham, G; Bushell, M; Wagner, SD; Willis, AE
- College Publications