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Cellular origin and pathophysiology of chronic lymphocytic leukemia
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- Marc Seifert
- Institute of Cell Biology (Cancer Research) 1 and 2
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- Ludger Sellmann
- Institute of Cell Biology (Cancer Research) 1 and 2
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- Johannes Bloehdorn
- Department of Internal Medicine III, University of Ulm, Ulm 89081, Germany 3
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- Frederik Wein
- Institute of Cell Biology (Cancer Research) 1 and 2
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- Stephan Stilgenbauer
- Department of Internal Medicine III, University of Ulm, Ulm 89081, Germany 3
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- Jan Dürig
- Institute of Cell Biology (Cancer Research) 1 and 2
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- Ralf Küppers
- Institute of Cell Biology (Cancer Research) 1 and 2
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Description
<jats:p>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.</jats:p>
Journal
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- Journal of Experimental Medicine
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Journal of Experimental Medicine 209 (12), 2183-2198, 2012-10-22
Rockefeller University Press
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Details 詳細情報について
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- CRID
- 1361699996235635712
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- ISSN
- 15409538
- 00221007
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- Data Source
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- Crossref