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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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Submitted April 12, 2005
Accepted October 19, 2005

Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes

Dirk Kienle, Axel Benner, Alexander Krober, Dirk Winkler, Daniel Mertens, Andreas Buhler, Till Seiler, Ulrich Jager, Peter Lichter, Hartmut Dohner, and Stephan Stilgenbauer*

Department of Internal Medicine III, University of Ulm, Ulm, Germany
Central Unit Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

* Corresponding author; email: stephan.stilgenbauer{at}medizin.uni-ulm.de.

The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in CLL. To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor 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: 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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