1. ¹Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
2. ²Department of Internal Medicine III, University of Ulm, Ulm, Germany
3. ³Department of Medical Biology, Medical University of Vienna, Vienna, Austria
4. ⁴Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria
5. ⁵Department of Medical Computer Sciences, Section of Clinical Biometrics, Medical University of Vienna, Vienna, Austria
6. ⁶Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria
7. ⁷Center of Molecular Medicine of the Austrian Academy of Sciences (CeMM), Vienna, Austria

Correspondence: Professor U Jäger, Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna 1090, Austria. Fax: +43 1 402 6930; E-mail: ulrich.jaeger@meduniwien.ac.at

Received 16 August 2004; Accepted 4 February 2005; Published online 28 April 2005.

Abstract

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 IGV_H 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.