Cellular origin and pathophysiology of chronic lymphocytic leukemia

• DOI: 10.1084/jem.20120833
• Publication Date: 2012-10-24T00:29:28Z
• Authors: Marc Seifert; Ludger Sellmann; Johannes Bloehdorn; Frederik Wein; Stephan Stilgenbauer; Jan Dürig; Ralf Küppers
• Keywords: CD5; Lymphocytosis

The cellular origin of chronic lymphocytic leukemia (CLL) is still debated, although this information critical to understanding its pathogenesis. Transcriptome analyses CLL and the main normal B cell subsets from human blood spleen revealed that immunoglobulin variable region (IgV) gene unmutated derives mature CD5+ cells mutated a distinct, previously unrecognized CD5+CD27+ post–germinal center subset. Stereotyped V rearrangements are enriched among cells, providing independent evidence for derivation CLL. Notably, these populations include oligoclonal expansions already found in young healthy adults, putatively representing an early phase development before precursor lesion monoclonal lymphocytosis. Finally, we identified deregulated proteins, including EBF1 KLF transcription factors, were not detected previous comparisons conventional cells.