Ribosome-associated nucleophosmin 1: increased expression and shuttling activity distinguishes prognostic subtypes in chronic lymphocytic leukaemia
| Autor: | David Y. Mason, Julie A. Adams, Anthony D. Whetton, Karen Pulford, Karen S. Rees-Unwin, Andrew R. Pettitt, Claire V. Hutchinson, Ann Marie Buckle, Guy S. Lucas, Philip J. Brown, Richard D. Unwin, Alison H. Banham, Robin Faragher, John Burthem, Suzanne M. Johnson |
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| Rok vydání: | 2010 |
| Předmět: |
Cytoplasm
Nucleolus Chronic lymphocytic leukemia DNA Mutational Analysis Somatic hypermutation Biology Gene mutation medicine.disease_cause Diagnosis Differential immune system diseases hemic and lymphatic diseases Biomarkers Tumor medicine Humans Cell Nucleus Regulation of gene expression Mutation Nucleophosmin Nucleoplasm integumentary system Nuclear Proteins DNA Neoplasm Hematology Prognosis medicine.disease Leukemia Lymphocytic Chronic B-Cell Neoplasm Proteins Up-Regulation Gene Expression Regulation Neoplastic Cancer research Somatic Hypermutation Immunoglobulin |
| Zdroj: | British Journal of Haematology. 148:534-543 |
| ISSN: | 1365-2141 0007-1048 |
| DOI: | 10.1111/j.1365-2141.2009.07979.x |
| Popis: | Two distinct groups of chronic lymphocytic leukaemia (CLL) are distinguished by the presence or absence of somatic hypermutation of the immunoglobulin heavy-chain gene. CLL without somatic hypermutation has an adverse outcome, but the precise biological differences that underlie this more aggressive clinical-course are unclear. Using a proteomic approach, we found that the two prognostic forms of CLL were consistently distinguished according to their protein expression pattern. The most important difference observed related to the different expression of nucleophosmin 1 between the two forms of CLL. This different expression was not related to apoptosis, proliferation or gene mutation. However, co-immunoprecipitation experiments identified an association between nucleophosmin 1 and ribosomal proteins. Using immunocytofluorescence, nucleophosmin 1 expression was identified in the nucleoli and nucleoplasm of all cells, but in a proportion of cells, nucleophosmin had been transferred from the nucleoplasm to the cytoplasm. Both the fluorescent intensity, and the frequency of cytoplasmic nucleophosmin 1 expression, was higher in CLL without somatic hypermutation. We propose therefore, that nucleophosmin 1, in association with ribosomal proteins, undergoes nucleo-cytoplasmic shuttling in CLL. This process is most prominent in un-mutated CLL and may signify altered protein biosynthesis. |
| Databáze: | OpenAIRE |
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