title: KLKB1 mRNA overexpression: A novel molecular biomarker for the diagnosis of chronic lymphocytic leukemia.
abstract: OBJECTIVE
  Plasma kallikrein, also known as Fletcher factor or kallikrein B1 (KLKB1), is a serine endopeptidase, like its homologs tissue kallikrein and kallikrein-related peptidases (KLKs). Its physiological role is to catalyze the release of kinins and other vasoactive peptides. Several KLKs have been proposed as putative tumor biomarkers with significant diagnostic and/or prognostic value in human malignancies arising from solid tumors; the most prominent example is the worldwide use of KLK3 (prostate-specific antigen, PSA) in prostate cancer diagnostics. The aim of this study was to analyze KLKB1 mRNA expression in B-cell chronic lymphocytic leukemia (CLL) patients and to examine its diagnostic value as a novel molecular biomarker in CLL.
  
  
  METHODS
  Total RNA was isolated from peripheral blood mononuclear cells of sixty-nine patients previously diagnosed with CLL and thirty-one healthy blood donors. After cDNA preparation, a sensitive and cost-effective quantitative real-time PCR (qRT-PCR) methodology was developed and applied for KLKB1 mRNA quantification. Last, we carried out a biostatistical analysis to assess the clinical significance of KLKB1 mRNA expression.
  
  
  RESULTS
  According to our findings, KLKB1 mRNA expression is significantly higher in CLL patients than in healthy blood donors. Furthermore, KLKB1 mRNA levels are negatively correlated with CD38 expression, an established prognostic biomarker in CLL. Most importantly, KLKB1 mRNA expression possesses important diagnostic value, distinguishing very efficiently CLL patients from non-leukemic population.
  
  
  CONCLUSIONS
  KLKB1 mRNA expression is a putative molecular biomarker in CLL, meriting investigation in large cohorts of CLL patients and non-leukemic controls.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Athens GR-15701, Greece.
authors.forename: Panagiotis G
authors.initials: PG
authors.lastname: Adamopoulos
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Athens GR-15701, Greece.
authors.forename: Christos K
authors.initials: CK
authors.lastname: Kontos
authors.affiliation: Second Department of Internal Medicine, Propaedeutic, University of Athens, University General Hospital "Attikon", Athens GR-12462, Greece.
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Papageorgiou
authors.affiliation: Second Department of Internal Medicine, Propaedeutic, University of Athens, University General Hospital "Attikon", Athens GR-12462, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pappa
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Athens GR-15701, Greece. Electronic address: ascorilas@biol.uoa.gr.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D018709:Statistics, Nonparametric; D020298:U937 Cells; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D051997:ADP-ribosyl Cyclase 1; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: CLL; Diagnosis; Diagnostic biomarker; Fletcher factor; Kallikrein B1; Kallikrein-related peptidases; Molecular biomarker; Plasma kallikrein; Real-time PCR; qRT-PCR