Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential

Journal of Hematology & Oncology
Ingrid SpaanVictor Peperzak

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. F...Continue Reading

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Apr 25, 2019·Annals of the New York Academy of Sciences·Noyel GhoshParames C Sil
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Methods Mentioned

BETA
GTPases
X-ray
protein folding
glycosylation
ubiquitination
xenograft
sumoylation
hyperubiquitination
xenografts
immunoprecipitation

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