title: Lipoprotein lipase is differentially expressed in prognostic subsets of chronic lymphocytic leukemia but displays invariably low catalytical activity.
abstract: 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<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<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.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden. mahmoud.mansouri@genpat.uu.se
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mansouri
authors.forename: Marie
authors.initials: M
authors.lastname: Sevov
authors.forename: Emma
authors.initials: E
authors.lastname: Fahlgren
authors.forename: Gerard
authors.initials: G
authors.lastname: Tobin
authors.forename: Mikael
authors.initials: M
authors.lastname: Jondal
authors.forename: Lyda
authors.initials: L
authors.lastname: Osorio
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D008071:Lipoprotein Lipase / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D008071:Lipoprotein Lipase