Analysis of LPL gene expression in patients with chronic lymphocytic leukemia

Abstract

Summary. Aim: 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 SF3B1 gene mutations. Materials and Methods: Expression of LPL mRNA was measured in peripheral blood mononuclear cells of 73 CLL 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. Results: 44 of 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 of NOTCH1 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 107 vs 143, p = 0.048) as well as in Binet A patients, albeit with borderline significance (median 139 vs not reached, p = 0.086). Conclusion: 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.

Genome-wide DNA methylation profiling in chronic lymphocytic leukaemia

“…These two proteins could activate the uptake of fatty acids and were highly expressed in a lipogenic cancer model ( Zaidi et al, 2013 ). LPL expression was reported to be closely correlated with IGHV mutational status and may be involved in BCR and NOTCH1 -dependent signalling pathways ( Bilous et al, 2019 ). Further studies are needed to decipher the role of lipid metabolism in CLL aetiology.…”

Cell Surface Lipoprotein Lipase Enzyme as A Prognostic Indicator in B-Cell Chronic Lymphocytic Leukemia

“…CLL cases with fully methylated LPL promoter sites were shown to have a significant clinical benefit with a more indolent disease course and longer times to initial treatment [38]. Abnormal expression of LPL has also been found to be associated with other pathways such as NOTCH-1 and B-cell receptor stereotypy [39]. Ultimately, the evidence behind LPL's genetic expression and the prognostic value of its cytoplasmic products is robust.…”

TP53 Gene 72 Arg/Pro (rs1042522) single nucleotide polymorphism increases the risk and the severity of chronic lymphocytic leukemia

“…The Arg variant appears to induce a stronger apoptosis response than the Pro variant ( 16 ). On the other hand, CLL patients with the Pro/Pro genotype are considered to be at an increased risk of developing other TP53 mutations ( 33 ).…”