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The multiple ways Wnt signaling contributes to acute leukemia pathogenesis
Sheila C Soares-Lima1, Maria S Pombo-de-Oliveira2, Flávia R G Carneiro3,4
1Epigenetics Group, Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
Journal of Leukocyte Biology
|June 24, 2020
Summary
Wnt signaling is crucial for normal blood formation and development. Its dysregulation, through various mechanisms, significantly contributes to acute leukemia, presenting therapeutic opportunities.
Area of Science:
- Molecular Biology
- Cell Signaling
- Hematology
Background:
- WNT proteins are conserved secreted glycoproteins vital for signaling in development and homeostasis.
- Wnt signaling operates through canonical (β-catenin-mediated) and noncanonical pathways (PCP, WNT/Ca++).
- Dysregulation of Wnt pathways is implicated in various diseases, including hematological malignancies.
Purpose of the Study:
- To review the role of Wnt signaling in normal hematopoiesis.
- To detail the dysregulation of canonical Wnt signaling in acute leukemia.
- To explore the therapeutic potential of targeting Wnt signaling in leukemia.
Main Methods:
- Literature review of Wnt signaling mechanisms.
- Analysis of Wnt pathway alterations in acute leukemia.
- Discussion of molecular drivers and therapeutic strategies.
Main Results:
- Wnt signaling is essential for normal hematopoietic stem cell function.
- Canonical Wnt signaling is frequently dysregulated in acute leukemia via gene expression, epigenetic, and mutational changes.
- These alterations impact different leukemia subtypes distinctly.
Conclusions:
- Wnt signaling plays a critical role in both normal hematopoiesis and acute leukemia pathogenesis.
- Targeting Wnt signaling offers potential therapeutic avenues for various forms of leukemia.
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