title: Decreased WNT3 expression in chronic lymphocytic leukaemia is a hallmark of disease progression and identifies patients with worse prognosis in the subgroup with mutated IGHV.
abstract: The canonical Wnt pathway, dependent on β-catenin-controlled transcription, is the most explored Wnt pathway, known to drive the malignant transformation of multiple cell types. Several reports have suggested that this pathway also participates in chronic lymphocytic leukaemia (CLL) pathogenesis. To get a better insight into the role of the Wnt/β-catenin pathway in CLL we analysed in detail the expression of the most overexpressed Wnt ligand, encoded by the WNT3 gene, in a well-defined cohort of 137 CLL patients. Our analysis demonstrated that (i) untreated patients with more aggressive disease (with a notable exception of patients with 11q deletion) express less WNT3, (ii) WNT3 declines with disease progression in a significant proportion of patients and (iii) low WNT3 was identified as a strong independent marker indicating shorter treatment-free survival in CLL patients with IGHV mutation. Interestingly, CLL-related lymphoid cell lines, but not stromal cells, failed to respond to the ligand-induced activation of the Wnt/β-catenin pathway. This opens the possibility that CLL cells use Wnt-3 to communicate with the cells in the microenvironment. We thus propose that the Wnt/β-catenin pathway plays a more complex role in CLL pathogenesis than previously anticipated.
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Poppova
authors.affiliation: Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Pavlina
authors.initials: P
authors.lastname: Janovska
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Karla
authors.initials: K
authors.lastname: Plevova
authors.affiliation: CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Radova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Plesingerova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Borsky
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Kotaskova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kantorova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Hlozkova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Figulova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.
authors.forename: Yvona
authors.initials: Y
authors.lastname: Brychtova
authors.affiliation: Department of Paediatric Otorhinolaryngology, University Hospital Brno and Medical Faculty, MU, Brno, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Machalova
authors.affiliation: Department of Paediatric Otorhinolaryngology, University Hospital Brno and Medical Faculty, MU, Brno, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Urik
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.affiliation: Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors.forename: Alois
authors.initials: A
authors.lastname: Kozubik
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Sarka
authors.initials: S
authors.lastname: Pavlova
authors.affiliation: Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Bryja
mesh_terms: D002450:Cell Communication; D002460:Cell Line; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D011379:Prognosis; D060449:Wnt Signaling Pathway; D060508:Wnt3 Protein / Q000235:genetics*
chemical_list: C555507:WNT3 protein, human; D060508:Wnt3 Protein
keywords: WNT3; Wnt/β-catenin pathway; chronic lymphocytic leukaemia; prognostic marker