Signaling pathways and bone marrow microenvironment in myelodysplastic neoplasms

Eleonora Ceneri, Alessia De Stefano, Irene Casalin, Carlo Finelli, Antonio Curti, Stefania Paolini, Sarah Parisi, Federica Ardizzoia, Gianluca Cristiano, Jaqueline Boultwood, James A. McCubrey, Pann Ghill Suh, Giulia Ramazzotti, Roberta Fiume, Stefano Ratti, Lucia Manzoli, Lucio Cocco, Matilde Y. Follo

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2 Citations (Scopus)
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Abstract

Key signaling pathways within the Bone Marrow Microenvironment (BMM), such as Notch, Phosphoinositide-Specific Phospholipase C (PI-PLCs), Transforming Growth Factor β (TGF-β), and Nuclear Factor Kappa B (NF-κB), play a vital role in the progression of Myelodysplastic Neoplasms (MDS). Among the various BMM cell types, Mesenchymal Stromal Cells (MSCs) are particularly central to these pathways. While these signaling routes can independently affect both MSCs and Hematopoietic Stem Cells (HSCs), they most importantly alter the dynamics of their interactions, leading to abnormal changes in survival, differentiation, and quiescence. Notch and PI-PLC signaling facilitate intercellular communication, TGF-β promotes quiescence and suppresses hematopoiesis, and NF-κB-driven inflammatory responses foster an environment detrimental to normal hematopoiesis. This review highlights the role of these pathways within the MDS microenvironment, driving the development and progression of the disease and paving the way for new possible therapeutic strategies.
Original languageEnglish
Article number101071
Number of pages6
JournalAdvances in Biological Regulation
Volume95
DOIs
Publication statusPublished - Jan 2025
Externally publishedYes

Keywords

  • Bone marrow microenvironment
  • Myelodysplastic neoplasms
  • NF-κB signaling
  • Notch signaling
  • Phosphoinositide signaling
  • TGF-β signaling

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