The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche

Paul Takam Kamga, Riccardo Bazzoni, Giada Dal Collo, Adriana Cassaro, Ilaria Tanasi, Anna Russignan, Cristina Tecchio, Mauro Krampera

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Abstract

Notch and Wnt signaling are highly conserved intercellular communication pathways involved in developmental processes, such as hematopoiesis. Even though data from literature support a role for these two pathways in both physiological hematopoiesis and leukemia, there are still many controversies concerning the nature of their contribution. Early studies, strengthened by findings from T-cell acute lymphoblastic leukemia (T-ALL), have focused their investigation on the mutations in genes encoding for components of the pathways, with limited results except for B-cell chronic lymphocytic leukemia (CLL); in because in other leukemia the two pathways could be hyper-expressed without genetic abnormalities. As normal and malignant hematopoiesis require close and complex interactions between hematopoietic cells and specialized bone marrow (BM) niche cells, recent studies have focused on the role of Notch and Wnt signaling in the context of normal crosstalk between hematopoietic/leukemia cells and stromal components. Amongst the latter, mesenchymal stromal/stem cells (MSCs) play a pivotal role as multipotent non-hematopoietic cells capable of giving rise to most of the BM niche stromal cells, including fibroblasts, adipocytes, and osteocytes. Indeed, MSCs express and secrete a broad pattern of bioactive molecules, including Notch and Wnt molecules, that support all the phases of the hematopoiesis, including self-renewal, proliferation and differentiation. Herein, we provide an overview on recent advances on the contribution of MSC-derived Notch and Wnt signaling to hematopoiesis and leukemia development.

Original languageEnglish
Article number599276
Pages (from-to)599276
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Publication statusPublished - 8 Jan 2021

Bibliographical note

Copyright © 2021 Takam Kamga, Bazzoni, Dal Collo, Cassaro, Tanasi, Russignan, Tecchio and Krampera.

Funding Information:
This work was supported by Fondazione CARIVERONA and the Interdepartmental Laboratory of Medical Research (LURM) at the University of Verona, Verona, Italy.

Publisher Copyright:
© Copyright © 2021 Takam Kamga, Bazzoni, Dal Collo, Cassaro, Tanasi, Russignan, Tecchio and Krampera.

Research programs

  • EMC OR-01

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