Micro‐environment alterations through time leading to myeloid malignancies

• Published in: British journal of pharmacology Vol. 181; no. 2; pp. 283 - 294
• Main Authors: Nyamondo, Kudzai, Wheadon, Helen
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-01-2024
• Subjects: ageing; Aging; Bone Marrow; bone marrow microenvironment; Cell Differentiation; haematopoiesis; Hematopoiesis; Hematopoietic Stem Cells; Hemopoiesis; Homeostasis; Inflammation; Malignancy; Microenvironments; ageing; bone marrow microenvironment; haematopoiesis
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.15924

The micro‐environment plays a critical role in haematopoietic stem cell (HSC) development, self‐renewal, differentiation and maintenance by providing a supportive cellular framework and essential molecular cues to sustain homeostasis. In ageing and development of age‐related clonal haematopoiesis, the combined contribution of intrinsic alterations in haematopoietic stem cells and their surrounding micro‐environment can promote myeloid skewing and release of pro‐inflammatory cytokines. A pro‐inflammatory micro‐environment is a common feature in the initiation and sustenance of several myeloid malignancies. Furthermore, remodelling of the micro‐environment is recognized to potentiate the survival of malignant over normal cells. This review explores micro‐environmental interactions in the haematopoietic system of adults, especially how the bone marrow micro‐environment is impacted by ageing, the onset of age‐related clonal haematopoiesis and the development of myeloid malignancies. In addition, we also discuss the possible role age‐related clonal haematopoiesis and chronic inflammatory conditions play in altering the bone marrow micro‐environment dynamics. Finally, we explore the importance of in vitro models that accurately mimic different aspects of the bone marrow micro‐environment in order to study normal and malignant haematopoiesis.
LINKED ARTICLES
This article is part of a themed issue on Cancer Microenvironment and Pharmacological Interventions. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.2/issuetoc