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Sökning: WFRF:(Sevov Marie)

  • Resultat 1-10 av 13
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1.
  • Kaderi, Mohd Arifin, et al. (författare)
  • LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia
  • 2011
  • Ingår i: Haematologica. - Ferrata Storti Foundation. - 1592-8721. ; 96:8, s. 1153-1160
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The 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 Methods Using 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. Results High 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. Conclusions LPL 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.
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  • Kaderi, Mohd Arifin, et al. (författare)
  • <em>LPL</em> is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia
  • 2011
  • Ingår i: Haematologica (online). - 0390-6078 .- 1592-8721. ; 96:8, s. 1153-1160
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong></p> <p>The 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.</p> <p><strong>DESIGN AND METHODS:</strong></p> <p>Using 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.</p> <p><strong>RESULTS:</strong></p> <p>High 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.</p> <p><strong>CONCLUSIONS:</strong></p> <p>LPL 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.</p>
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  • Mansouri, Mahmoud, et al. (författare)
  • Lipoprotein lipase is differentially expressed in prognostic subsets of chronic lymphocytic leukemia but displays invariably low catalytical activity
  • 2010
  • Ingår i: Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis. - 0145-2126 .- 1873-5835. ; 34:3, s. 301-306
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Lipoprotein lipase (LPL) expression has been shown to correlate with IGHV mutational status and to predict outcome in chronic lymphocytic leukemia (CLL). We here investigated the prognostic impact of LPL expression in relation to other prognostic markers including IGHV3-21 usage in 140 CLL patients. Additionally, we studied the catalytic activity of LPL in CLL cells. A significant difference in LPL mRNA expression was detected in IGHV unmutated compared to mutated CLL patients (p&lt;0.001). However, the poor-prognostic mutated/stereotyped IGHV3-21 patients did not differ from other mutated CLL cases. Clinical outcome was significantly different in CLL cases with high versus low LPL expression (p&lt;0.001), and LPL expression exceeded mutation status/IGHV3-21 usage as an independent prognostic marker. Finally, LPL protein expression correlated significantly with mRNA expression and was higher in IGHV unmutated versus mutated CLL (p=0.018), although the majority of synthesized protein was catalytically inactive indicating a non-catalytical function in CLL.</p>
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6.
  • Mansouri, Mahmoud, et al. (författare)
  • Lipoprotein lipase is differentially expressed in prognostic subsets of chronic lymphocytic leukemia but displays invariably low catalytical activity
  • 2010
  • Ingår i: Leukemia research. - Elsevier. - 1873-5835. ; 34:3, s. 301-306
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Lipoprotein lipase (LPL) expression has been shown to correlate with IGHV mutational status and to predict outcome in chronic lymphocytic leukemia (CLL). We here investigated the prognostic impact of LPL expression in relation to other prognostic markers including IGHV3-21 usage in 140 CLL patients. Additionally, we studied the catalytic activity of LPL in CLL cells. A significant difference in LPL mRNA expression was detected in IGHV unmutated compared to mutated CLL patients (p&lt;0.001). However, the poor-prognostic mutated/stereotyped IGHV3-21 patients did not differ from other mutated CLL cases. Clinical outcome was significantly different in CLL cases with high versus low LPL expression (p&lt;0.001), and LPL expression exceeded mutation status/IGHV3-21 usage as an independent prognostic marker. Finally, LPL protein expression correlated significantly with mRNA expression and was higher in IGHV unmutated versus mutated CLL (p=0.018), although the majority of synthesized protein was catalytically inactive indicating a non-catalytical function in CLL.</p>
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7.
  • Mansouri, Mahmoud R, et al. (författare)
  • IGHV3-21 gene usage is associated with high TCL1 expression in chronic lymphocytic leukemia
  • 2010
  • Ingår i: European Journal of Haematology. - 0902-4441 .- 1600-0609. ; 84:2, s. 109-116
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>T-cell leukemia/lymphoma protein 1 (TCL1) was recently shown to display an expression pattern in chronic lymphocytic leukemia (CLL) corresponding to molecular subtypes, where poor-risk patients demonstrated higher expression levels. Here, we examined the mRNA expression pattern of TCL1 in 144 patients with CLL, including 67 immunoglobulin heavy-chain variable (IGHV) mutated, 58 IGHV unmutated and 19 patients with IGHV3-21 usage. A higher TCL1 expression level was detected in patients with CLL with unmutated vs. mutated IGHV genes (P &lt; 0.001), whereas no difference was demonstrated within the IGHV3-21 cohort (i.e., mutated vs. unmutated and stereotyped vs. non-stereotyped complementarity determining region 3). The IGHV3-21 subgroup displayed high TCL1 mRNA expression, differing significantly from other IGHV mutated cases (P &lt; 0.001), although 11/19 had mutated IGHV genes. Furthermore, high TCL1 expression levels were associated with significantly shorter overall survival (P &lt; 0.001). Altogether, we show that TCL1 mRNA expression may predict clinical outcome in CLL and that the IGHV3-21 subset, regardless of mutational status, displays high TCL1 expression.</p>
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8.
  • Sevov, Marie, et al. (författare)
  • Longitudinal study of RNA-based prognostic markers in chronic lymphocytic leukemia reveals <em>LPL</em> as the most stable
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • <p>Several genes display differential expression in prognostic subsets in chronic lymphocytic leukemia (CLL), including <em>LPL</em>, <em>TCL1</em>, <em>ZAP70</em> and <em>MCL1</em>. CLL patients commonly have an indolent course with low stage disease and long survival, and in this study we aimed to investigate the stability of RNA-based prognostic markers in such an indolent cohort over time. mRNA expression of <em>LPL</em>, <em>TCL1</em>, <em>ZAP70</em> and <em>MCL1</em> was measured in sequential unsorted samples obtained from 96 CLL patients at both diagnosis and a median follow-up of seven years. <em>LPL</em> was the only RNA-based marker that did not demonstrate any significant changes in expression in diagnostic vs. follow-up samples. Furthermore, an 82% concordance between both time-points was observed when grouping cases based on high or low expression. <em>LPL</em> expression was not affected by treatment and in addition, <em>LPL</em> expression in follow-up samples could predict overall survival. In contrast, <em>TCL1</em> expression was found to increase at follow-up, especially in cases displaying low expression at diagnosis. As TCL1 promotes cell survival this increase could possibly be of importance for progression of the disease. Both <em>ZAP70</em> and <em>MCL1</em> mRNA expression were found to vary significantly during the disease course. In summary, using unsorted CLL samples, we have demonstrated that <em>LPL</em> is superior to other RNA-based markers based on stability over time. These findings fully endorse the use of <em>LPL</em> analysis at any time point of the disease.</p>
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9.
  • Sevov, Marie, et al. (författare)
  • Resveratrol regulates the expression of LXR-alpha in human macrophages
  • 2006
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 348:3, s. 1047-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The naturally occurring polyphenol resveratrol has been associated with the beneficial effects of red wine consumption on cardiovascular disease and shown to inhibit atherosclerosis in animal models. To determine if resveratrol affects the expression of genes that control lipid homeostasis in human macrophages, we measured expression changes in the LXR-alpha pathway, crucial to cholesterol efflux, and in genes that mediate lipoprotein uptake. Resveratrol treatment of THP-1 macrophages induced LXR-alpha at mRNA and protein levels. Increased recruitment of RNA polymerase 11 to the LXR-alpha promoter suggested that up-regulation was at least partly mediated by transcriptional mechanisms. Resveratrol also induced LXR-alpha in human monocyte-derived macrophages together with elevated ABCAI and ABCGI mRNA levels. Moreover, resveratrol repressed the expression of the lipid uptake genes LPL and SR-All. The ability of resveratrol to modulate expression of the genes involved in lipid uptake and efflux suggests that polyphenols can potentially limit cholesterol accumulation in human macrophages.</p>
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10.
  • Sevov, Marie, et al. (författare)
  • RNA-based markers as prognostic factors in chronic lymphocytic leukemia
  • 2012
  • Ingår i: Expert Review of Hematology. - 1747-4086 .- 1747-4094. ; 5:1, s. 69-79
  • Forskningsöversikt (refereegranskat)abstract
    • <p>Chronic lymphocytic leukemia (CLL) is most often indolent at diagnosis but has a highly variable clinical course, and many patients will eventually progress and require treatment. Currently, there are a number of clinical and molecular markers known to be predictive of prognosis in CLL that can be applied to discriminate patients that are more likely to develop a progressive disease. Gene-expression profiling studies have identified genes with differential expression between prognostic subgroups in CLL, and research on these RNA-based prognostic markers has expanded during recent years. For example, high lipoprotein lipase and CLLU1 mRNA expression have recently been shown to be strong markers of poor clinical outcome. In this review we will provide a summary of the most significant prognostic markers in CLL, focusing on the recent category of RNA-based markers in particular.</p>
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