title: COBLL1, LPL and ZAP70 expression defines prognostic subgroups of chronic lymphocytic leukemia patients with high accuracy and correlates with IGHV mutational status.
abstract: The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. Patients with unmutated IGHV (U-CLL) usually progress rapidly, whereas patients with mutated IGHV (M-CLL) have a more indolent disease. The expression of several genes correlates closely with the IGHV mutational status and could be used to assess prognosis in CLL. We analyzed the prognostic relevance of COBLL1, LPL, and ZAP70 gene expression, which correlated with IGHV mutational status (p < 0.0001), in 117 CLL patients and established a prognostic parameter dividing the tested cohort according to the disease aggressiveness. Our prognostic parameter was validated on an independent cohort of 161 CLL patients and achieved a high accuracy (94%). Patients divided according to the prognostic parameter differ in overall survival and time to first treatment (p < 0.0001, HR  = 2.300/5.970, 95% CI: 1.587-3.450/4.621-15.86). Our approach provides a reliable alternative method to prognosis assessment via IGHV mutational status analysis.
authors.affiliation: a Center of Molecular Medicine, Central European Institute of Technology, Masaryk University , Brno , Czech Republic.|b Department of Internal Medicine - Hematology and Oncology, Faculty of Medicine , Masaryk University and University Hospital Brno , Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Plesingerova
authors.affiliation: c GENERI BIOTECH s.r.o , Hradec Kralove , Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Librova
authors.affiliation: a Center of Molecular Medicine, Central European Institute of Technology, Masaryk University , Brno , Czech Republic.|b Department of Internal Medicine - Hematology and Oncology, Faculty of Medicine , Masaryk University and University Hospital Brno , Czech Republic.
authors.forename: Karla
authors.initials: K
authors.lastname: Plevova
authors.affiliation: c GENERI BIOTECH s.r.o , Hradec Kralove , Czech Republic.
authors.forename: Antonin
authors.initials: A
authors.lastname: Libra
authors.affiliation: a Center of Molecular Medicine, Central European Institute of Technology, Masaryk University , Brno , Czech Republic.
authors.forename: Boris
authors.initials: B
authors.lastname: Tichy
authors.affiliation: b Department of Internal Medicine - Hematology and Oncology, Faculty of Medicine , Masaryk University and University Hospital Brno , Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Skuhrova Francova
authors.affiliation: d 4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove , University Hospital Hradec Kralove and Charles University , Hradec Kralove , Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Vrbacky
authors.affiliation: d 4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove , University Hospital Hradec Kralove and Charles University , Hradec Kralove , Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Smolej
authors.affiliation: a Center of Molecular Medicine, Central European Institute of Technology, Masaryk University , Brno , Czech Republic.|b Department of Internal Medicine - Hematology and Oncology, Faculty of Medicine , Masaryk University and University Hospital Brno , Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
authors.affiliation: e Department of Cytokinetics, Institute of Biophysics , Academy of Sciences of the Czech Republic , Brno , Czech Republic.|f Institute of Experimental Biology, Faculty of Science , Masaryk University , Brno , Czech Republic.
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Bryja
authors.affiliation: a Center of Molecular Medicine, Central European Institute of Technology, Masaryk University , Brno , Czech Republic.|b Department of Internal Medicine - Hematology and Oncology, Faculty of Medicine , Masaryk University and University Hospital Brno , Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.affiliation: a Center of Molecular Medicine, Central European Institute of Technology, Masaryk University , Brno , Czech Republic.|b Department of Internal Medicine - Hematology and Oncology, Faculty of Medicine , Masaryk University and University Hospital Brno , Czech Republic.
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C584084:COBLL1 protein, human; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D014157:Transcription Factors; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C548261:LPL protein, human; D008071:Lipoprotein Lipase
keywords: COBLL1; Chronic lymphocytic leukemia; IGHV mutational status; LPL; ZAP70; prognosis