Author:
Stranneheim Henrik,Orre Lukas M,Lehtiö Janne,Flygare Jenny
Abstract
Abstract
Background
B-cell lymphomas are thought to reflect different stages of B-cell maturation. Based on cytogenetics and molecular markers, mantle cell lymphoma (MCL) is presumed to derive predominantly from naïve, pre-germinal centre (pre-GC) B lymphocytes. The aim of this study was to develop a method to investigate the similarity between MCL cells and different B-cell compartments on a protein expression level.
Methods
Subpopulations of B cells representing the germinal centre (GC), the pre-GC mantle zone and the post-GC marginal zone were isolated from tonsils using automated magnetic cell sorting (AutoMACS) of cells based on their expression of CD27 and IgD. Protein profiling of the B cell subsets, of cell lines representing different lymphomas and of primary MCL samples was performed using top-down proteomics profiling by surface-enhanced laser detection/ionization time-of-flight mass spectrometry (SELDI-TOF-MS).
Results
Quantitative MS data of significant protein peaks (p-value < 0.05) separating the three B-cell subpopulations were generated. Together, hierarchical clustering and principal component analysis (PCA) showed that the primary MCL samples clustered together with the pre- and post-GC subpopulations. Both primary MCL cells and MCL cell lines were clearly separated from the B cells representing the GC compartment.
Conclusion
AutoMACS sorting generates sufficient purity to enable a comparison between protein profiles of B cell subpopulations and malignant B lymphocytes applying SELDI-TOF-MS. Further validation with an increased number of patient samples and identification of differentially expressed proteins would enable a search for possible treatment targets that are expressed during the early development of MCL.
Publisher
Springer Science and Business Media LLC
Subject
Molecular Biology,Biochemistry
Reference25 articles.
1. Leich E, Hartmann EM, Burek C, Ott G, Rosenwald A: Diagnostic and prognostic significance of gene expression profiling in lymphomas. APMIS 2007,115(10):1135–1146. 10.1111/j.1600-0463.2007.apm_867.xml.x
2. Lim MS, Elenitoba-Johnson KS: Mass spectrometry-based proteomic studies of human anaplastic large cell lymphoma. Mol Cell Proteomics 2006,5(10):1787–1798. 10.1074/mcp.R600005-MCP200
3. Fan G, Molstad M, Braziel RM, Standley M, Huang J, Rodgers W, Nagalla S: Proteomic profiling of mature CD10+ B-cell lymphomas. Am J Clin Pathol 2005,124(6):920–929. 10.1309/UEDXPHAAP740B61D
4. Jansen C, Hebeda KM, Linkels M, Grefte JM, Raemaekers JM, van Krieken JH, Groenen PJ: Protein profiling of B-cell lymphomas using tissue biopsies: A potential tool for small samples in pathology. Cell Oncol 2008,30(1):27–38.
5. Wright GL Jr: SELDI proteinchip MS: a platform for biomarker discovery and cancer diagnosis. Expert Rev Mol Diagn 2002,2(6):549–563. 10.1586/14737159.2.6.549
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