Microenvironment alterations through time leading to myeloid malignancies

The microenvironment 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 (ARCH), the combined contribution of intrinsic alterations in HSCs and their surrounding microenvironment can promote myeloid skewing and release of pro-inflammatory cytokines. A pro-inflammatory microenvironment is a common feature in the initiation and sustenance of several myeloid malignancies. Furthermore, remodelling of the microenvironment is recognised to potentiate the survival of malignant over normal cells. This review explores microenvironmental interactions in the haematopoietic system of adults, especially how the bone marrow (BM) microenvironment is impacted by ageing, the onset of ARCH and the development of myeloid malignancies. In addition, we also discuss the possible role inflammageing and chronic inflammatory conditions play in altering the BM microenvironment dynamics. Finally, we explore the importance of in vitro models that accurately recapitulate different aspects of the BM microenvironment in order to study normal and malignant haematopoiesis