title: Rel a is an independent biomarker of clinical outcome in chronic lymphocytic leukemia.
abstract: OBJECTIVE
  We recently demonstrated the biologic importance of the nuclear factor kappa B (NF-kappaB) subunit Rel A in chronic lymphocytic leukemia (CLL) and hypothesized that Rel A DNA binding would have prognostic significance in this disease.
  
  
  METHODS
  Rel A DNA binding was quantified in nuclear extracts derived from 131 unselected CLL patient samples using a quantitative DNA-binding enzyme-linked immunosorbent assay-based method. We then investigated the ability of Rel A to predict for the requirement for treatment and survival and compared our findings with other established prognostic markers.
  
  
  RESULTS
  Rel A DNA binding was strongly associated with advanced Binet stage (P < .0001) but did not correlate with immunoglobulin V(H) (IgV(H)) mutation status (P = .25), CD38 expression (P = .87), or zeta-chain-associated protein kinase 70 (ZAP-70) expression (P = .55). It was predictive of time to first treatment (P = .02) and time to subsequent treatment (P = .0001). In addition, Rel A was the most predictive marker of survival both from date of diagnosis (hazard ratio [HR], 9.1; P = .01) and date of entry into the study (HR, 3.9; P = .05) and retained prognostic significance in multivariate analysis for both time to first treatment and overall survival in the presence of Binet stage, IgV(H) mutation status, CD38, and ZAP-70.
  
  
  CONCLUSIONS
  Rel A is an independent prognostic marker of survival in CLL and seems to have the unique capacity to predict the duration of response to therapy. Prospective assessment of Rel A as a marker of clinical outcome and as a therapeutic target are now warranted.
authors.affiliation: Department of Haematology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors.forename: Saman
authors.initials: S
authors.lastname: Hewamana
authors.forename: Thet Thet
authors.initials: TT
authors.lastname: Lin
authors.forename: Clare
authors.initials: C
authors.lastname: Rowntree
authors.forename: Kamaraj
authors.initials: K
authors.lastname: Karunanithi
authors.forename: Guy
authors.initials: G
authors.lastname: Pratt
authors.forename: Robert
authors.initials: R
authors.lastname: Hills
authors.forename: Chris
authors.initials: C
authors.lastname: Fegan
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Chris
authors.initials: C
authors.lastname: Pepper
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000401:mortality*; D008875:Middle Aged; D011379:Prognosis; D051996:Transcription Factor RelA / Q000235:genetics*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D007135:Immunoglobulin Variable Region; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1