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Decreased WNT 3 expression in chronic lymphocytic leukaemia is a hallmark of disease progression and identifies patients with worse prognosis in the subgroup with mutated IGHV
Author(s) -
Poppova Lucie,
Janovska Pavlina,
Plevova Karla,
Radova Lenka,
Plesingerova Hana,
Borsky Marek,
Kotaskova Jana,
Kantorova Barbara,
Hlozkova Michaela,
Figulova Jana,
Brychtova Yvona,
Machalova Michaela,
Urik Milan,
Doubek Michael,
Kozubik Alois,
Pospisilova Sarka,
Pavlova Sarka,
Bryja Vitezslav
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14312
Subject(s) - wnt signaling pathway , cancer research , ighv@ , lrp5 , beta catenin , stromal cell , catenin , biology , chronic lymphocytic leukemia , pathogenesis , immunology , medicine , signal transduction , microbiology and biotechnology , leukemia
Summary 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 WNT 3 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 WNT 3 , (ii) WNT 3 declines with disease progression in a significant proportion of patients and (iii) low WNT 3 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.