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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2904-2911.
Prepublished online as a Blood First Edition Paper on December 8, 2005; DOI 10.1182/blood-2005-07-2615.


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Submitted July 1, 2005
Accepted November 15, 2005

Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia

Anne Mette Buhl*, Jesper Jurlander, Flemming S Jorgensen, Anne Marie Ottesen, Jack B Cowland, Lise Mette Gjerdrum, Brian V Hansen, and Henrik Leffers

The Leukemia Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark
Department of Medicinal Chemistry, Danish University of Pharmaceutical Sciences, Copenhagen, Denmark
University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
The Granulocyte Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark
Department of Pathology, Rigshospitalet, Copenhagen, Denmark

* Corresponding author; email: am.buhl{at}get2net.dk.

The pathogenesis of chronic lymphocytic leukemia (CLL) is unknown, but may involve aberrant activation of signaling pathways. Somatic hypermutations in rearranged immunoglobulin heavy chain (IgVH) genes allow a division of CLL patients into two categories; mutated IgVH genes are associated with an indolent disease, whereas unmutated IgVH genes define an aggressive form. Using differential display to compare gene expression in CLL cells with and without IgVH hypermutations, we identified a novel gene, CLL Upregulated gene1 (CLLU1) that was highly upregulated in CLL cells without IgVH hypermutations. CLLU1 mapped to chromosome 12q22, within a cluster of genes that are active in germinal center B-cells. However, appreciable levels of CLLU1 were only detectable in CLL cells, and not in a panel of normal tissue extracts, nor in any other tested hematological malignancy. High expression of CLLU1 in CLL samples occurred irrespective of trisomy 12 or large chromosomal rearrangements. CLLU1 encodes six mRNAs with no sequence homology to any known gene, and most transcripts appear to be non-coding. Two transcripts, however, potentially encode a peptide with remarkable structural similarity to human IL-4. These data, in particular the unique and restricted expression pattern, suggest that CLLU1 is the first disease specific gene identified in CLL.


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