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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2090-2093.
Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-04-1483.
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NEOPLASIA
Brief report
Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes
Dirk Kienle,
Axel Benner,
Alexander Kröber,
Dirk Winkler,
Daniel Mertens,
Andreas Bühler,
Till Seiler,
Ulrich Jäger,
Peter Lichter,
Hartmut Döhner, and
Stephan Stilgenbauer
From the Department of Internal Medicine III, University of Ulm; Central Unit Biostatistics, German Cancer Research Center (DKFZ), Heidelberg; Division of Molecular Genetics, DKFZ Heidelberg, Germany; and Department of Internal Medicine I, Medical University of Vienna, Austria.
The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in chronic lymphocytic leukemia (CLL). To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor (BCR) signaling/activation, cell cycle, and apoptosis control in CLL using these specific VH genes compared to VH mutated (VH-MUT) and VH unmutated (VH-UM) CLL not using these VH genes. V3-21 cases showed characteristic expression differences compared to VH-MUT (up: ZAP70 [or ZAP-70]; down: CCND2, P27) and VH-UM (down: PI3K, CCND2, P27, CDK4, BAX) involving several BCR-related genes. Similarly, there was a marked difference between VH unmutated cases using the V1-69 gene and VH-UM (up: FOS; down: BLNK, SYK, CDK4, TP53). Therefore, usage of specific VH genes appears to have a strong influence on the gene expression pattern pointing to antigen recognition and ongoing BCR stimulation as a pathogenic factor in these CLL subgroups.
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