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Tumor Biology
Published in: Tumor Biology 9/2016

01-09-2016 | Original Article

Dishevelled proteins are significantly upregulated in chronic lymphocytic leukaemia

Authors: Abdul Salam Khan, Mohammad Hojjat-Farsangi, Amir Hossein Daneshmanesh, Lotta Hansson, Parviz Kokhaei, Anders Österborg, Håkan Mellstedt, Ali Moshfegh

Published in: Tumor Biology | Issue 9/2016

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Abstract

Dishevelled (DVL) proteins are components of the Wnt signalling pathways, and increased expression is associated with various malignancies. Information on DVLs in chronic lymphatic leukaemia (CLL) is limited. The aim of the present study was to investigate the role of DVLs in CLL cells and association with Wnt pathways downstream of ROR1. DVL1, 2 and 3 were exclusively expressed in CLL cells as compared to normal peripheral blood mononuclear cells (PBMCs). The expression of DVL1 and DVL3 proteins was significantly more pronounced in progressive than in non-progressive disease (p < 0.01), whereas the level of DVL2 was significantly higher in non-progressive as compared to progressive disease (p < 0.001). Treatment of CLL cells with anti-ROR1 specific monoclonal antibodies induced dephosphorylation of ROR1 as well as of tyrosine and serine residues of both DVL2 and DVL3. However, gene silencing of DVLs in the CLL cell line (EHEB) did not induce detectable apoptosis. Non-progressive CLL patients had a different protein activity pattern with regard to Wnt signalling pathway proteins as GSK-3β, β-catenin and AKT as compared to progressive disease. The DVL2 protein may play a role in the activation of signalling pathways in CLL during early stages of the disease, while DVL1 and 3 may have a role in later phases of the leukaemia.
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Metadata
Title
Dishevelled proteins are significantly upregulated in chronic lymphocytic leukaemia
Authors
Abdul Salam Khan
Mohammad Hojjat-Farsangi
Amir Hossein Daneshmanesh
Lotta Hansson
Parviz Kokhaei
Anders Österborg
Håkan Mellstedt
Ali Moshfegh
Publication date
01-09-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 9/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5039-5

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