Lipoprotein lipase mRNA expression in whole blood is a prognostic marker in B cell chronic lymphocytic leukemia

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 the 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 (LPL) mRNA expression 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 expression 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. (c) 2007 American Association for Clinical Chemistry