Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia.
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.
Buhl
Anne Mette
AM
Department of Hematology, 4041, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, DK. am.buhl@get2net.dk
Jurlander
Jesper
J
Jørgensen
Flemming S
FS
Ottesen
Anne Marie
AM
Cowland
Jack B
JB
Gjerdrum
Lise Mette
LM
Hansen
Brian V
BV
Leffers
Henrik
H
D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding
C510032:CLLU1 lncRNA, human; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding