title: LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.
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.
  
  
  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.
authors.affiliation: Dept. of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Mohd Arifin
authors.initials: MA
authors.lastname: Kaderi
authors.forename: Meena
authors.initials: M
authors.lastname: Kanduri
authors.forename: Anne Mette
authors.initials: AM
authors.lastname: Buhl
authors.forename: Marie
authors.initials: M
authors.lastname: Sevov
authors.forename: Nicola
authors.initials: N
authors.lastname: Cahill
authors.forename: Rebeqa
authors.initials: R
authors.lastname: Gunnarsson
authors.forename: Mattias
authors.initials: M
authors.lastname: Jansson
authors.forename: Karin Ekström
authors.initials: KE
authors.lastname: Smedby
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjalgrim
authors.forename: Jesper
authors.initials: J
authors.lastname: Jurlander
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Larry
authors.initials: L
authors.lastname: Mansouri
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; C548261:LPL protein, human; D008071:Lipoprotein Lipase