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

TY - JOUR

T1 - Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia

AU - Buhl, Anne Mette

AU - Jurlander, Jesper

AU - Jørgensen, Flemming Steen

AU - Ottesen, Anne Marie

AU - Cowland, Jack B

AU - Gjerdrum, Lise Mette

AU - Hansen, Brian V

AU - Leffers, Henrik

PY - 2006

Y1 - 2006

N2 - 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 2 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 up-regulated gene 1 (CLLU1), that was highly up-regulated 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 detectable only in CLL cells and not in a panel of normal tissue extracts or in any other tested hematologic malignancy. High expression of CLLU1 in CLL samples occurred irrespective of trisomy 12 or large chromosomal rearrangements. CLLU1 encodes 6 mRNAs with no sequence homology to any known gene, and most transcripts appear to be noncoding. Two transcripts, however, potentially encode a peptide with remarkable structural similarity to human interleukin 4. These data, in particular the unique and restricted expression pattern, suggest that CLLU1 is the first disease-specific gene identified in CLL.

AB - 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 2 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 up-regulated gene 1 (CLLU1), that was highly up-regulated 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 detectable only in CLL cells and not in a panel of normal tissue extracts or in any other tested hematologic malignancy. High expression of CLLU1 in CLL samples occurred irrespective of trisomy 12 or large chromosomal rearrangements. CLLU1 encodes 6 mRNAs with no sequence homology to any known gene, and most transcripts appear to be noncoding. Two transcripts, however, potentially encode a peptide with remarkable structural similarity to human interleukin 4. These data, in particular the unique and restricted expression pattern, suggest that CLLU1 is the first disease-specific gene identified in CLL.

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 12

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Immunoglobulin Heavy Chains

KW - Immunoglobulin Variable Region

KW - Leukemia, Lymphocytic, Chronic, B-Cell

KW - Mutation

KW - Neoplasm Proteins

U2 - 10.1182/blood-2005-07-2615

DO - 10.1182/blood-2005-07-2615

M3 - Journal article

C2 - 16339396

SN - 0006-4971

VL - 107

SP - 2904

EP - 2911

JO - Blood

JF - Blood

IS - 7

ER -