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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism
-
Cell Nucleolus / metabolism
-
Down-Regulation / genetics
-
Eukaryotic Initiation Factors / genetics
-
Eukaryotic Initiation Factors / metabolism
-
Gene Expression Profiling*
-
Gene Expression Regulation, Leukemic
-
Humans
-
Immunoblotting
-
Leukemia, Lymphocytic, Chronic, B-Cell / blood*
-
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
-
Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
-
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism
-
Polyribosomes / metabolism
-
Protein Biosynthesis
-
RNA, Ribosomal / metabolism
-
Ribosomal Proteins / genetics
-
Ribosomal Proteins / metabolism
-
Ribosomes / metabolism*
-
Survival Analysis
-
Treatment Outcome
Substances
-
Cell Cycle Proteins
-
DKC1 protein, human
-
Eukaryotic Initiation Factors
-
Nuclear Proteins
-
RNA, Ribosomal
-
Ribosomal Proteins