title: Lipoprotein lipase expression is a novel prognostic factor in B-cell chronic lymphocytic leukemia.
abstract: B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course. Recent studies have shown that expression of lipoprotein lipase (LPL) and ADAM29 may serve as novel prognostic markers in B-CLL. To investigate the prognostic value of these genes, we quantified their expression in peripheral blood mononuclear cells using quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) in a cohort of 133 B-CLL patients and correlated the results with clinical outcome, and other known prognostic factors. LPL, ADAM29, LPL and ADAM29 ratios, as well as CD38 and ZAP-70 protein expression determined by multiparameter flow cytometry, were predictive of treatment-free survival. Multivariate Cox regression analysis identified LPL, ADAM29 and CD38 as independent prognostic markers. Evaluation of several disease characteristics in association with the LPL expression status of the patients' B-CLL cells showed highly significant differences for CD38 and ZAP-70 expression, suggesting a correlation of LPL expression with these established adverse prognostic factors. Sequential RQ-PCR analyses in a subset of 22 patients revealed that LPL mRNA expression was relatively stable in the majority of patients, whereas ADAM29 expression levels varied substantially over time. Furthermore, in a subgroup analysis, LPL provided prognostic information in both early stage (Binet A) and patients with more advanced disease (Binet B and C). Conversely, high ADAM29 expression was predictive of a long treatment-free interval in Binet stage A but did not retain its prognostic significance in Binet B and C patients. The LPL/ADAM29 expression ratio was not found to be an independent prognostic factor and did not offer any advantages over the use of LPL alone. Collectively, our data confirm a role for LPL as a novel prognostic indicator in B-CLL.
authors.affiliation: Department of Hematology, University Hospital Essen, Essen, Germany. holger.nueckel@uni-essen.de
authors.forename: Holger
authors.initials: H
authors.lastname: Nückel
authors.forename: Andreas
authors.initials: A
authors.lastname: Hüttmann
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: Roland
authors.initials: R
authors.lastname: Schroers
authors.forename: Anja
authors.initials: A
authors.lastname: Führer
authors.forename: Ludger
authors.initials: L
authors.lastname: Sellmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis*; D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis
chemical_list: D051746:ZAP-70 Protein-Tyrosine Kinase; D008071:Lipoprotein Lipase; D051997:ADP-ribosyl Cyclase 1; D051722:ADAM Proteins; C122189:ADAM29 protein, human