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Clinical Chemistry 0: clinchem.2006.076331v2, 2006; 10.1373/clinchem.2006.076331
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Received on July 14, 2006
Accepted on November 7, 2006

Molecular Diagnostics and Genetics

Lipoprotein Lipase mRNA in Whole Blood Is a Prognostic Marker in B Cell Chronic Lymphocytic Leukemia

Femke Van Bockstaele 1, Valerie Pede 1, Ann Janssens 2, Filip Callewaert 1, Fritz Offner 2, Bruno Verhasselt 1, Jan Philippé 1*

1 Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium
2 Department of Internal Medicine, Ghent University, Ghent, Belgium

* To whom correspondence should be addressed. E-mail: Jan.Philippe{at}UGent.be.

Background: Chronic lymphocytic leukemia (CLL) is characterized by high individual variability in clinical course and the need for therapy. Differentiation of prognostic subgroups is based primarily on the mutation status of the genes for the variable region of immunoglobulin heavy chain (IGHV). The time- and labor-intensive nature of this analysis necessitates the use of easily applicable surrogate markers.

Methods: We developed a quantitative PCR (qPCR) method for determining lipoprotein lipase gene (LPL) mRNA levels and analyzed samples of lysed whole blood and CD19-selected cells from 50 CLL patients. Associations of LPL and ZAP70 [{zeta}-chain (TCR) associated protein kinase 70 kDa] expression with IGHV mutation status, overall survival (OS) and treatment-free survival (TFS) were investigated.

Results: Lysed samples of whole blood and CD19-selected cells were similar with respect to LPL expression (R = 0.88; P <0.0001). LPL expression was significantly associated with IGHV mutation status [{chi}2(1) = 15.3; P <0.0001] and showed an 89.3% specificity, a 68.2% sensitivity, an 83.3% positive predictive value, and a 78.1% negative predictive value for IGHV mutation status. LPL expression was significantly associated with both OS and TFS in log-rank tests (both P values = 0.002). LPL-positive patients had a significantly shorter median TFS time (23 months) than LPL-negative patients (88 months) (P = 0.002).

Conclusions: LPL mRNA level is a valuable prognostic marker in CLL. The method does not require cell purification, and its applicability with archived samples facilitates its use in the clinical routine and other studies.


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