title: Cellular origin and pathophysiology of chronic lymphocytic leukemia.
abstract: The cellular origin of chronic lymphocytic leukemia (CLL) is still debated, although this information is critical to understanding its pathogenesis. Transcriptome analyses of CLL and the main normal B cell subsets from human blood and spleen revealed that immunoglobulin variable region (IgV) gene unmutated CLL derives from unmutated mature CD5(+) B cells and mutated CLL derives from a distinct, previously unrecognized CD5(+)CD27(+) post-germinal center B cell subset. Stereotyped V gene rearrangements are enriched among CD5(+) B cells, providing independent evidence for a CD5(+) B cell derivation of CLL. Notably, these CD5(+) B cell populations include oligoclonal expansions already found in young healthy adults, putatively representing an early phase in CLL development before the CLL precursor lesion monoclonal B cell lymphocytosis. Finally, we identified deregulated proteins, including EBF1 and KLF transcription factors, that were not detected in previous comparisons of CLL and conventional B cells.
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen 45122, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Seifert
authors.forename: Ludger
authors.initials: L
authors.lastname: Sellmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Bloehdorn
authors.forename: Frederik
authors.initials: F
authors.lastname: Wein
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D018956:CD5 Antigens / Q000378:metabolism; D016000:Cluster Analysis; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D008218:Lymphocytosis / Q000235:genetics*; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics; D025341:Principal Component Analysis; D015534:Trans-Activators / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D018956:CD5 Antigens; C081976:EBF1 protein, human; D007135:Immunoglobulin Variable Region; D051741:Kruppel-Like Transcription Factors; D009841:Oligonucleotides; D015534:Trans-Activators; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C080774:erythroid Kruppel-like factor