Lipoprotein lipase is differentially expressed in prognostic subsets of chronic lymphocytic leukemia but displays invariably low catalytical activity

Mansouri, Mahmoud; Sevov, Marie; Fahlgren, Emma; Tobin, Gerard; Jondal, Mikael; Osorio, Lyda M.; Roos, Göran; Olivecrona, Gunilla; Rosenquist, Richard

doi:10.1016/j.leukres.2009.07.032

Cited by 33 publications

(40 citation statements)

References 25 publications

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“…For example, LPL is not expressed in normal B cells and found in very low levels in CD19 negative cells in CLL patients. 15,22 Moreover, differences found in TCL1A expression were negligible when comparing sorted versus unsorted CLL samples from the same patients. 17 Finally, CLLU1 expression has previously been reported to be restricted to CLL tumor cells.…”

Section: Discussionmentioning

confidence: 97%

“…Lipoprotein lipase (LPL), initially identified in gene expression profiling of CLL, is one of the most differentially expressed genes in IGHV mutated versus unmutated CLL, where it is significantly higher expressed in unmutated cases. [13][14][15] In addition, T-cell leukemia/lymphoma 1 (TCL1A), 16,17 CLLupregulated gene-1 (CLLU1) 18,19 and myeloid cell factor-1 (MCL1) 20 have also been found to display higher expression in unmutated CLL patients. Moreover, high expression of these markers at the protein and/or mRNA transcription level has been associated with inferior treatment-free and overall survival (OS) in a number of independent CLL cohorts.…”

Section: Introductionmentioning

confidence: 99%

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LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia

Kaderi¹,

Kanduri²,

Buhl³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThe expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Design and MethodsUsing real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. ResultsHigh expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. ConclusionsLPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.Key words: LPL, RNA-based markers, chronic lymphocytic leukemia, prognosis.Citation: Kaderi MA, Kanduri M, Buhl AM, Sevov M, Cahill N, Gunnarsson R, Jansson M, Smedby KE, Hjalgrim H, Jurlander J, Juliusson G, Mansouri L, and Rosenquist R. LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia

Kaderi¹,

Kanduri²,

Buhl³

et al. 2011

Haematologica

View full text Add to dashboard Cite

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“…Bridging may involve different cell types, requiring LPL dimerization and HSPG on both surfaces [13]. Accordingly, expression of LPL by malignant cells may promote tumorigenesis by enabling the cell–stromal interactions that are critical for tumor maintenance [13, 14]. In fact, LPL is overexpressed in squamous cell carcinomas of the cervix and may be associated with increased tumor aggressiveness, likely secondary to the non-catalytic function of LPL [13].…”

Section: Discussionmentioning

confidence: 99%

Association between differential gene expression and body mass index among endometrial cancers from The Cancer Genome Atlas Project

Roque

Makowski

Chen

et al. 2016

Gynecologic Oncology

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Objective The Cancer Genome Atlas (TCGA) identified four integrated clusters for endometrial cancer (EC): POLE, MSI, CNL and CNH. We evaluated differences in gene expression profiles of obese and non-obese women with EC and examined the association of body mass index (BMI) within the clusters identified in TCGA. Methods TCGA RNAseq data was used to identify genes related to increasing BMI among ECs. The POLE, MSI and CNL clusters were composed mostly of endometrioid EC. Patient BMI was compared between these three clusters with one-way ANOVA. Association between gene expression and BMI was also assessed while adjusting for confounding effects of potential confounding factors. p-values testing the association between gene expression and BMI were adjusted for multiple hypothesis testing over the 20,531 genes considered. Results Mean BMI was statistically different between the ECs in the CNL (35.8) versus POLE (29.8) cluster (p=0.006) and approached significance for the MSI (33.0) versus CNL (35.8) cluster (p=0.05). 181 genes were significantly up- or down-regulated with increasing BMI in endometrioid EC (q-value<0.01), including LPL, IRS-1, IGFBP4, IGFBP7 and the progesterone receptor. DAVID functional annotation analysis revealed significant enrichment in "cell cycle" (adjusted p-value=1.5E-5) and "DNA metabolic processes" (adjusted p-value=1E-3) for the identified genes. Conclusions Obesity related genes were found to be upregulated with increasing BMI among endometrioid ECs. Patients with POLE tumors have the lowest median BMI when compared to MSI and CNL. Given the heterogeneity amongst endometrioid EC, consideration should be giving to abandoning the Type I and II classification of EC tumors.

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“…Most impressively, patients with chronic lymphocytic leukemia (CLL) whose leukemia cells express high levels of LPL transcripts have a lower survival rate (Van Bockstaele et al 2007;Maloum et al 2009;Kaderi et al 2011). One study indicated that high LPL transcript levels in CLL are associated with increased LPL protein production; however, enzymatic activity assays suggested that much of the LPL could be inactive (Mansouri et al 2010). At this point, it is unclear whether LPL levels are simply a useful prognostic indicator for CLL or whether the high levels of LPL expression directly affect the behavior of the tumor cells.…”

Section: Lipolysis In Cancer and Cancer Cachexiamentioning

confidence: 99%

Biochemistry and pathophysiology of intravascular and intracellular lipolysis

2013

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All organisms use fatty acids (FAs) for energy substrates and as precursors for membrane and signaling lipids. The most efficient way to transport and store FAs is in the form of triglycerides (TGs); however, TGs are not capable of traversing biological membranes and therefore need to be cleaved by TG hydrolases (“lipases”) before moving in or out of cells. This biochemical process is generally called “lipolysis.” Intravascular lipolysis degrades lipoprotein-associated TGs to FAs for their subsequent uptake by parenchymal cells, whereas intracellular lipolysis generates FAs and glycerol for their release (in the case of white adipose tissue) or use by cells (in the case of other tissues). Although the importance of lipolysis has been recognized for decades, many of the key proteins involved in lipolysis have been uncovered only recently. Important new developments include the discovery of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), the molecule that moves lipoprotein lipase from the interstitial spaces to the capillary lumen, and the discovery of adipose triglyceride lipase (ATGL) and comparative gene identification-58 (CGI-58) as crucial molecules in the hydrolysis of TGs within cells. This review summarizes current views of lipolysis and highlights the relevance of this process to human disease.

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Lipoprotein lipase is differentially expressed in prognostic subsets of chronic lymphocytic leukemia but displays invariably low catalytical activity

Cited by 33 publications

References 25 publications

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia

Association between differential gene expression and body mass index among endometrial cancers from The Cancer Genome Atlas Project

Biochemistry and pathophysiology of intravascular and intracellular lipolysis

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