1. ¹Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
2. ²Ludwig Boltzmann Institute for Clinical and Experimental Oncology, Vienna, Austria
3. ³Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna; Vienna, Austria
4. ⁴Department of Statistics and Probability Theory, Vienna University of Technology, Vienna, Austria
5. ⁵Department of Internal Medicine III, University of Ulm, Ulm, Germany
6. ⁶Department of Medicine, Harvard Medical School, Boston, MA, USA
7. ⁷Institute of Immunology, Medical University of Vienna, Vienna, Austria

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

⁸These authors contributed equally to this work.

Received 8 September 2005; Revised 21 February 2006; Accepted 27 February 2006; Published online 13 April 2006.

Abstract

Lipoprotein lipase (LPL) is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL) related to immunoglobulin V_H gene (IgV_H)mutational status. We determined gene expression profiles using Affymetrix U133A GeneChips in two groups of B-CLLs selected for either high ('LPL+', n=10) or low ('LPL-', n=10) LPL mRNA expression. Selected genes were verified by real-time PCR in an extended patient cohort (n=42). A total of 111 genes discriminated LPL+ from LPL- B-CLLs. Of these, the top three genes associated with time to first treatment were Septin10, DMD and Gravin (P0.01). The relationship of LPL+ and LPL- B-CLL gene expression signatures to 52 tissues was statistically analyzed. The LPL+ B-CLL expression signature, represented by 64 genes was significantly related to fat, muscle and PB dendritic cells (P<0.001). Exploration of microarray data to define functional alterations related to the biology of LPL+ CLL identified two functional modules, fatty acid degradation and MTA3 signaling, as being altered with higher statistical significance. Our data show that LPL+ B-CLL cells have not only acquired gene expression changes in fat and muscle-associated genes but also in functional pathways related to fatty acid degradation and signaling which may ultimately influence CLL biology and clinical outcome.