title: Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis.
abstract: BACKGROUND
  B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.
  
  
  METHODS
  We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.
  
  
  RESULTS
  Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.
  
  
  CONCLUSIONS
  This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.
authors.affiliation: MRC-HPA Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Chadeau-Hyam
authors.forename: R C H
authors.initials: RC
authors.lastname: Vermeulen
authors.forename: D G A J
authors.initials: DG
authors.lastname: Hebels
authors.forename: R
authors.initials: R
authors.lastname: Castagné
authors.forename: G
authors.initials: G
authors.lastname: Campanella
authors.forename: L
authors.initials: L
authors.lastname: Portengen
authors.forename: R S
authors.initials: RS
authors.lastname: Kelly
authors.forename: I A
authors.initials: IA
authors.lastname: Bergdahl
authors.forename: B
authors.initials: B
authors.lastname: Melin
authors.forename: G
authors.initials: G
authors.lastname: Hallmans
authors.forename: D
authors.initials: D
authors.lastname: Palli
authors.forename: V
authors.initials: V
authors.lastname: Krogh
authors.forename: R
authors.initials: R
authors.lastname: Tumino
authors.forename: C
authors.initials: C
authors.lastname: Sacerdote
authors.forename: S
authors.initials: S
authors.lastname: Panico
authors.forename: T M C M
authors.initials: TM
authors.lastname: de Kok
authors.forename: M T
authors.initials: MT
authors.lastname: Smith
authors.forename: J C S
authors.initials: JC
authors.lastname: Kleinjans
authors.forename: P
authors.initials: P
authors.lastname: Vineis
authors.forename: S A
authors.initials: SA
authors.lastname: Kyrtopoulos
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D015894:Genome, Human; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D025341:Principal Component Analysis; D011446:Prospective Studies; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor
keywords: chronic lymphocytic leukemia; epidemiology; lymphoma; mRNA analyses; prospective cohort