ABSTRACT
Lipoprotein lipase (LPL) is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL) related to immunoglobulin V(H) gene (IgV(H))mutational status. We determined gene expression profiles using Affymetrix U133A GeneChips in two groups of B-CLLs selected for either high ('LPL+', n=10) or low ('LPL-', n=10) LPL mRNA expression. Selected genes were verified by real-time PCR in an extended patient cohort (n=42). A total of 111 genes discriminated LPL+ from LPL- B-CLLs. Of these, the top three genes associated with time to first treatment were Septin10, DMD and Gravin (P
Subject(s)
Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Leukemic , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/enzymology , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Lipoprotein Lipase/genetics , Cohort Studies , Cytoskeletal Proteins/genetics , Dystrophin/genetics , Fatty Acids/genetics , Fatty Acids/metabolism , GTP Phosphohydrolases/genetics , Gene Expression Profiling , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Lipoprotein Lipase/biosynthesis , Mutation , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , SeptinsABSTRACT
Individual mouse strains differ significantly in terms of behaviour, cognitive function and long-term potentiation. Hippocampal gene expression profiling of eight different mouse strains points towards strain-specific regulation of genes involved in neuronal information storage. Protein expression with regard to strain- dependent expression of structures related to neuronal information storage has not been investigated yet. Herein, a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry (MALDI-TOF/TOF) has been chosen to address this question by determining strain-dependent expression of proteins involved in neurotransmission and activity-induced actin remodelling in hippocampal tissue of five mouse strains. Of 31 spots representing 16 different gene products analysed and quantified, N-ethylmaleimide-sensitive fusion protein, N-ethylmaleimide-sensitive factor attachment protein-alpha, actin-like protein 3, profilin and cofilin were expressed in a strain-dependent manner. By treating protein expression as a phenotype, we have shown significant genetic variation in brain protein expression. Further experiments in this direction may provide an indication of the genetic elements that contribute to the phenotypic differences between the selected strains through the expressional level of the translated protein. In view of this, we propose that proteomic analysis enabling to concomitantly survey the expression of a large number of proteins could serve as a valuable tool for genetic and physiological studies of central nervous system function.
