title: High expression of lipoprotein lipase in poor risk B-cell chronic lymphocytic leukemia.
abstract: We investigated the pattern of lipoprotein lipase (LPL) expression in B-cell chronic lymphocytic leukemia (B-CLL) and assessed its prognostic relevance. Expression of LPL mRNA as well as protein was highly restricted to leukemic B cells. The intensity of intracellular immunoreactivity of LPL was higher in samples of patients with unmutated immunoglobulin heavy-chain variable region genes (IGV(H)) compared to those with mutated IGV(H) genes. LPL mRNA levels in peripheral blood mononuclear cells (PBMNC) from 104 CLL patients differed by 1.5 orders of magnitude between cases with mutated (N=51) or unmutated (N=53) IGV(H) (median: 1.33 vs 45.22 compared to normal PBMNC). LPL expression correlated strongly with IGV(H) mutational status (R=0.614; P<0.0001). High LPL expression predicted unmutated IGV(H) status with an odds ratio of 25.90 (P<0.0001) and discriminated between mutated and unmutated cases in 87 of 104 patients (84%). LPL expression was higher in patients with poor risk cytogenetics. High LPL expression was associated with a shorter treatment-free survival (median 40 vs 96 months, P=0.001) and a trend for a shorter median overall survival (105 months vs not reached). Our data establish LPL as a prognostic marker and suggest functional consequences of LPL overexpression in patients with B-CLL.
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Heintel
authors.forename: D
authors.initials: D
authors.lastname: Kienle
authors.forename: M
authors.initials: M
authors.lastname: Shehata
authors.forename: A
authors.initials: A
authors.lastname: Kröber
authors.forename: E
authors.initials: E
authors.lastname: Kroemer
authors.forename: I
authors.initials: I
authors.lastname: Schwarzinger
authors.forename: D
authors.initials: D
authors.lastname: Mitteregger
authors.forename: T
authors.initials: T
authors.lastname: Le
authors.forename: A
authors.initials: A
authors.lastname: Gleiss
authors.forename: C
authors.initials: C
authors.lastname: Mannhalter
authors.forename: A
authors.initials: A
authors.lastname: Chott
authors.forename: J
authors.initials: J
authors.lastname: Schwarzmeier
authors.forename: C
authors.initials: C
authors.lastname: Fonatsch
authors.forename: A
authors.initials: A
authors.lastname: Gaiger
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.forename: S
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: U
authors.initials: U
authors.lastname: Jäger
mesh_terms: D002869:Chromosome Aberrations; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000201:enzymology*; D008071:Lipoprotein Lipase / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D008071:Lipoprotein Lipase