Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia
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Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia. / Buhl, Anne Mette; Jurlander, Jesper; Jørgensen, Flemming Steen; Ottesen, Anne Marie; Cowland, Jack B; Gjerdrum, Lise Mette; Hansen, Brian V; Leffers, Henrik.
I: Blood, Bind 107, Nr. 7, 2006, s. 2904-11.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
VL - 107
SP - 2904
EP - 2911
JO - Blood
JF - Blood
SN - 0006-4971
IS - 7
ER -
ID: 38393658