Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential
Abstract Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-018-0615-3 |
| _version_ | 1830416736294273024 |
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| author | Ingrid Spaan Reinier A. Raymakers Anja van de Stolpe Victor Peperzak |
| author_facet | Ingrid Spaan Reinier A. Raymakers Anja van de Stolpe Victor Peperzak |
| author_sort | Ingrid Spaan |
| collection | DOAJ |
| description | Abstract Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic bone disease, which is associated with bone pain and pathological fractures and was reported to facilitate disease progression. More recently, cumulative evidence also indicates the importance of intrinsic Wnt signaling in the survival of multiple myeloma cells. However, Wnt pathway-activating gene mutations could not be identified. The search for factors or processes responsible for Wnt pathway activation currently focuses on aberrant ligand levels in the bone marrow microenvironment, increased expression of Wnt transcriptional co-factors and associated micro-RNAs, and disturbed epigenetics and post-translational modification processes. Furthermore, Wnt pathway activation is associated with acquired cell adhesion-mediated resistance of multiple myeloma cells to conventional drug therapies, including doxorubicin and lenalidomide. In this review, we present an overview of the relevance of Wnt signaling in multiple myeloma and highlight the Wnt pathway as a potential therapeutic target for this disease. |
| first_indexed | 2024-12-20T21:29:27Z |
| format | Article |
| id | doaj.art-54b27bb2a10b45318f428f2e08fc63e5 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-20T21:29:27Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-54b27bb2a10b45318f428f2e08fc63e52022-12-21T19:26:05ZengBMCJournal of Hematology & Oncology1756-87222018-05-0111111810.1186/s13045-018-0615-3Wnt signaling in multiple myeloma: a central player in disease with therapeutic potentialIngrid Spaan0Reinier A. Raymakers1Anja van de Stolpe2Victor Peperzak3Laboratory of Translational Immunology, University Medical Center UtrechtDepartment of Hematology, University Medical Center UtrechtMolecular Diagnostics, Philips ResearchLaboratory of Translational Immunology, University Medical Center UtrechtAbstract Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic bone disease, which is associated with bone pain and pathological fractures and was reported to facilitate disease progression. More recently, cumulative evidence also indicates the importance of intrinsic Wnt signaling in the survival of multiple myeloma cells. However, Wnt pathway-activating gene mutations could not be identified. The search for factors or processes responsible for Wnt pathway activation currently focuses on aberrant ligand levels in the bone marrow microenvironment, increased expression of Wnt transcriptional co-factors and associated micro-RNAs, and disturbed epigenetics and post-translational modification processes. Furthermore, Wnt pathway activation is associated with acquired cell adhesion-mediated resistance of multiple myeloma cells to conventional drug therapies, including doxorubicin and lenalidomide. In this review, we present an overview of the relevance of Wnt signaling in multiple myeloma and highlight the Wnt pathway as a potential therapeutic target for this disease.http://link.springer.com/article/10.1186/s13045-018-0615-3Multiple myelomaWnt signalingβ-cateninOsteolytic bone diseaseDrug resistanceTargeted therapy |
| spellingShingle | Ingrid Spaan Reinier A. Raymakers Anja van de Stolpe Victor Peperzak Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential Journal of Hematology & Oncology Multiple myeloma Wnt signaling β-catenin Osteolytic bone disease Drug resistance Targeted therapy |
| title | Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential |
| title_full | Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential |
| title_fullStr | Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential |
| title_full_unstemmed | Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential |
| title_short | Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential |
| title_sort | wnt signaling in multiple myeloma a central player in disease with therapeutic potential |
| topic | Multiple myeloma Wnt signaling β-catenin Osteolytic bone disease Drug resistance Targeted therapy |
| url | http://link.springer.com/article/10.1186/s13045-018-0615-3 |
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