Micro-environment alterations through time leading to myeloid malignancies

Abstract

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.