High expression of lipoprotein lipase in poor risk B-cell chronic lymphocytic leukemia

被引:126
作者
Heintel, D
Kienle, D
Shehata, M
Kröber, A
Kroemer, E
Schwarzinger, I
Mitteregger, D
Le, T
Gleiss, A
Mannhalter, C
Chott, A
Schwarzmeier, J
Fonatsch, C
Gaiger, A
Döhner, H
Stilgenbauer, S
Jäger, U
机构
[1] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, A-1090 Vienna, Austria
[2] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany
[3] Med Univ Vienna, Dept Med Biol, A-1090 Vienna, Austria
[4] Med Univ Vienna, Dept Clin Chem & Lab Med, A-1090 Vienna, Austria
[5] Med Univ Vienna, Dept Med Comp Sci, Sect Clin Biometr, A-1090 Vienna, Austria
[6] Med Univ Vienna, Dept Clin Pathol, A-1090 Vienna, Austria
[7] Austrian Acad Sci, CeMM, Ctr Mol Med, A-1010 Vienna, Austria
关键词
lipoprotein lipase; prognostic factor; B-CLL;
D O I
10.1038/sj.leu.2403748
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We investigated the pattern of lipoprotein lipase (LPL) expression in B- cell chronic lymphocytic leukemia (B-CLL) and assessed its prognostic relevance. Expression of LPL mRNA as well as protein was highly restricted to leukemic B cells. The intensity of intracellular immunoreactivity of LPL was higher in samples of patients with unmutated immunoglobulin heavy-chain variable region genes (IGV(H)) compared to those with mutated IGV(H) genes. LPL mRNA levels in peripheral blood mononuclear cells (PBMNC) from 104 CLL patients differed by 1.5 orders of magnitude between cases with mutated (N = 51) or unmutated (N = 53) IGV(H) (median: 1.33 vs 45.22 compared to normal PBMNC). LPL expression correlated strongly with IGVH mutational status (R = 0.614; P < 0.0001). High LPL expression predicted unmutated IGV(H) status with an odds ratio of 25.90 (P < 0.0001) and discriminated between mutated and unmutated cases in 87 of 104 patients (84%). LPL expression was higher in patients with poor risk cytogenetics. High LPL expression was associated with a shorter treatment-Free survival (median 40 vs 96 months, P = 0.001) and a trend for a shorter median overall survival (105 months vs not reached). Our data establish LPL as a prognostic marker and suggest functional consequences of LPL overexpression in patients with B-CLL.
引用
收藏
页码:1216 / 1223
页数:8
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