Analysis of LPL gene expression in patients with chronic lymphocytic leukemia

Abstract

The IGHV mutational status is one of the most important markers for chronic lymphocytic leukemia(CLL) prognostication. Lipoprotein lipase(LPL) gene expression was found to correlate with IGHV status and was suggested as its surrogate marker. Recent data reported that LPL expression might be influenced by pivotal signalling pathways in CLL. This study aimed to assess LPL gene expression in relation to key immunogenetic and molecular markers of CLL, including IGHV mutational status, B-cell receptor (BCR) stereotypy, TP53, NOTCH1, and SF3B1gene mutations. Materials andMethods: Expression of LPL mRNA was measured in peripheral blood mononuclear cells of 73CLL patients by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). IGHV, NOTCH1, TP53, and SF3B1 gene mutation analysis was performed by PCR amplification and direct sequencing. 44of 73 (60%) CLL cases were categorized as LPL-positive based on the cut-off value established by ROC (receiver operating characteristic) curve analysis. LPL expression was significantly associated with IGHV mutation status (r=0.684; p < 0.0001) and tended to correlate with presence ofNOTCH1 gene mutations (p = 0.113). BCR stereotyped cases showed higher LPL expression values in comparison to unstereotyped cases in the LPL-positive group of patients (p=0.041). LPL expression was associated with a shorter overall survival in the entire СLL group (median 107vs 143, p=0.048) as well as in Binet A patients, albeit with borderline significance (median 139vs not reached, p=0.086). LPL expression was found to be closely correlated with IGHV gene mutational status and overall survival, proving LPL as prognostic marker in CLL. Our results also indicate a possible relationship between aberrant expression of LPL and BCR- and NOTCH1-dependent signalling pathways.