Mechanobiology and Primary Cilium in the Pathophysiology of Bone Marrow Myeloproliferative Diseases

Int J Mol Sci. 2024 Aug 14;25(16):8860. doi: 10.3390/ijms25168860.

Abstract

Philadelphia-Negative Myeloproliferative neoplasms (MPNs) are a diverse group of blood cancers leading to excessive production of mature blood cells. These chronic diseases, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), can significantly impact patient quality of life and are still incurable in the vast majority of the cases. This review examines the mechanobiology within a bone marrow niche, emphasizing the role of mechanical cues and the primary cilium in the pathophysiology of MPNs. It discusses the influence of extracellular matrix components, cell-cell and cell-matrix interactions, and mechanosensitive structures on hematopoietic stem cell (HSC) behavior and disease progression. Additionally, the potential implications of the primary cilium as a chemo- and mechanosensory organelle in bone marrow cells are explored, highlighting its involvement in signaling pathways crucial for hematopoietic regulation. This review proposes future research directions to better understand the dysregulated bone marrow niche in MPNs and to identify novel therapeutic targets.

Keywords: bone marrow niche; hematopoietic stem cells; mechanobiology; mesenchymal stromal cells; myeloproliferative neoplasms; primary cilium.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Cilia* / metabolism
  • Cilia* / pathology
  • Extracellular Matrix / metabolism
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Mechanotransduction, Cellular
  • Myeloproliferative Disorders* / metabolism
  • Myeloproliferative Disorders* / pathology
  • Myeloproliferative Disorders* / physiopathology
  • Signal Transduction