期刊
CELL DEATH & DISEASE
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2016.148
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资金
- LLR
- MRC
- HSH. Prince Albert II of Monaco
- Government of the Principality of Monaco
- MRC [MC_UP_A600_1024, MC_U132670597, MC_UP_A600_1023] Funding Source: UKRI
- Medical Research Council [MC_UP_A600_1024, MC_UP_A600_1023, MC_U132670597] Funding Source: researchfish
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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