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

A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment
A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment
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.
2041-4889
1-10
Sbarrato, T.
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Horvilleur, E.
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Poyry, T.
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Hill, K.
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Chaplin, L.C.
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Spriggs, R.V.
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Stoneley, M.
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Wilson, L.
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Jayne, S.
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Vulliamy, T.
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Beck, D.
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Dokal, I.
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Dyer, M.J.S.
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Yeomans, A.M.
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Packham, G.
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Bushell, M.
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Wagner, S.D.
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Willis, A.E.
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Sbarrato, T.
d8a19c5c-1671-4b15-b653-a6331289d580
Horvilleur, E.
12e13062-61c5-45b8-ad3b-dfe8f90d313e
Poyry, T.
ecca548b-df3a-4f1b-80d5-8566415ea051
Hill, K.
bd570b53-57c8-4a24-aad7-c5012db565e1
Chaplin, L.C.
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Spriggs, R.V.
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Stoneley, M.
cc01703b-098a-49f5-b79c-07fe33a721d0
Wilson, L.
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Jayne, S.
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Vulliamy, T.
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Beck, D.
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Dokal, I.
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Dyer, M.J.S.
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Yeomans, A.M.
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Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Bushell, M.
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Wagner, S.D.
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Willis, A.E.
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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)

Record type: Article

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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Accepted/In Press date: 2 May 2016
e-pub ahead of print date: 2 June 2016
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 404867
URI: http://eprints.soton.ac.uk/id/eprint/404867
ISSN: 2041-4889
PURE UUID: 23fd4cd0-9d1a-4d6a-89f1-35b685e93433
ORCID for G. Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 24 Jan 2017 14:19
Last modified: 16 Mar 2024 03:14

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Contributors

Author: T. Sbarrato
Author: E. Horvilleur
Author: T. Poyry
Author: K. Hill
Author: L.C. Chaplin
Author: R.V. Spriggs
Author: M. Stoneley
Author: L. Wilson
Author: S. Jayne
Author: T. Vulliamy
Author: D. Beck
Author: I. Dokal
Author: M.J.S. Dyer
Author: A.M. Yeomans
Author: G. Packham ORCID iD
Author: M. Bushell
Author: S.D. Wagner
Author: A.E. Willis

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