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

被引:46
作者
Buhl, AM
Jurlander, J
Jorgensen, FS
Ottesen, AM
Cowland, JB
Gjerdrum, LM
Hansen, BV
Leffers, H
机构
[1] Danish Univ Pharmaceut Sci, Dept Med, Copenhagen, Denmark
[2] Rigshosp, Dept Growth & Reprod, DK-2100 Copenhagen, Denmark
[3] Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark
[4] Rigshosp, Dept Hematol, Granulocyte Lab, DK-2100 Copenhagen, Denmark
[5] Rigshosp, Dept Hematol, Granulocyte Lab, DK-2100 Copenhagen, Denmark
[6] Rigshosp, Leukemia Lab, DK-2100 Copenhagen, Denmark
关键词
D O I
10.1182/blood-2005-07-2615
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The pathogenesis of chronic lymphocytic leukemia (CLL) is unknown but may involve aberrant activation of signaling pathways. Somatic hypermutations in rearranged immunoglobulin heavy-chain (IgV(H)) genes allow a division of CLL patients into 2 categories: mutated IgV(H) genes are associated with an indolent disease, whereas unmutated IgV(H) genes define an aggressive form. Using differential display to compare gene expression in CLL cells with and without IgV(H) hypermutations, we identified a novel gene, CLL up-regulated gene 1 (CLLU1), that was highly up-regulated in CLL cells without IgV(H) 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.
引用
收藏
页码:2904 / 2911
页数:8
相关论文
共 46 条
[1]  
BUHL AM, 2006, EUR J HAEMATOL 0102
[2]  
Burger JA, 2000, BLOOD, V96, P2655
[3]   INTERFERON GAMMA INHIBITS APOPTOTIC CELL-DEATH IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA [J].
BUSCHLE, M ;
CAMPANA, D ;
CARDING, SR ;
RICHARD, C ;
HOFFBRAND, AV ;
BRENNER, MK .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (01) :213-218
[4]   B-cell chronic lymphocytic leukemia: A bird of a different feather [J].
Caligaris-Cappio, F ;
Hamblin, TJ .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (01) :399-408
[5]  
*COMP CT METH REL, ABI PRISM 7900HT SEQ, pE11
[6]   Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia [J].
Damle, RN ;
Wasil, T ;
Fais, F ;
Ghiotto, F ;
Valetto, A ;
Allen, SL ;
Buchbinder, A ;
Budman, D ;
Dittmar, K ;
Kolitz, J ;
Lichtman, SM ;
Schulman, P ;
Vinciguerra, VP ;
Rai, KR ;
Ferrarini, M ;
Chiorazzi, N .
BLOOD, 1999, 94 (06) :1840-1847
[7]   INTERLEUKIN-4 PROTECTS CHRONIC LYMPHOCYTIC LEUKEMIC B-CELLS FROM DEATH BY APOPTOSIS AND UP-REGULATES BCL-2 EXPRESSION [J].
DANCESCU, M ;
RUBIOTRUJILLO, M ;
BIRON, G ;
BRON, D ;
DELESPESSE, G ;
SARFATI, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (05) :1319-1326
[8]  
Dierlamm J, 1997, GENE CHROMOSOME CANC, V20, P155, DOI 10.1002/(SICI)1098-2264(199710)20:2<155::AID-GCC6>3.0.CO
[9]  
2-2
[10]   Genomic aberrations and survival in chronic lymphocytic leukemia. [J].
Döhner, H ;
Stilgenbauer, S ;
Benner, A ;
Leupolt, E ;
Kröber, A ;
Bullinger, L ;
Döhner, K ;
Bentz, M ;
Lichter, P .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (26) :1910-1916