title: Association ofBaxExpression andBcl2/BaxRatio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia.
abstract: BACKGROUND
  In chronic lymphocytic leukemia (CLL),in vivoapoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which theBcl2family members play a central role.
  
  
  OBJECTIVE
  The aim of this study was to investigate the association of pro-apoptoticBaxgene expression andBcl2/Baxratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression.
  
  
  METHODS
  We analyzed the expression ofBaxmRNA andBcl2/BaxmRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction.
  
  
  RESULTS
  We detected significantBaxgene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevatedBcl2/Baxratio (p=<0.001). Regarding the association with prognostic markers, theBcl2/Baxratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-levelBaxexpression was associated withLPL-positive status (p=0.035). Both the expression ofBaxandBcl2/Baxratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance.
  
  
  CONCLUSIONS
  Our results suggest that dysregulated expression ofBcl2andBax, which leads to a highBcl2/Baxratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Ksenija
authors.initials: K
authors.lastname: Vucicevic
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jakovljevic
authors.affiliation: Hematology Clinic, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Colovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Tosic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Kostic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Irena
authors.initials: I
authors.lastname: Glumac
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Teodora
authors.initials: T
authors.lastname: Karan-Djurasevic
authors.affiliation: Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Colovic
keywords: Bax; Bcl2/Bax ratio; apoptosis; chronic lymphocytic leukemia; expression analysis