Abstract
Haematopoiesis is the term used to describe the production of blood cells. This is a tightly regulated hierarchical system in which mature circulating blood cells develop from a small population of haematopoietic stem (HSC) and progenitor cells within the microenvironment of the bone marrow. Molecular and genetic abnormalities arising in these stem cells lead to a block in the normal programme of proliferation and differentiation and result in the development of the blood cancers known as the leukaemias and lymphomas. Recently the regulatory role of the bone marrow microenvironment or niche has also become increasingly recognised. The interface between the bone and bone marrow (endosteum) and the region surrounding the blood vessels (perivascular) provide distinct niches harbouring quiescent HSC or proliferative HSC respectively. Current chemotherapeutic regimes can often successfully target the proliferative HSC but disease relapse occurs due to residual quiescent HSC. Understanding these developmental and regulatory processes and the associated cell communication mechanisms are thus crucial to the development of new treatment strategies. The CCN family of proteins have been recognised to play a key role in all aspects of haematopoiesis.
Highlights
Haematopoiesis is the term used to describe the production of blood cells
Specific regions or niches within the marrow are associated with distinct stem cell populations and this in turn is due to the stromal cell populations present and the regulatory molecules which they produce
Our current concept of haematopoiesis is that of a hierarchical structure in which a small number of multipotent stem cells develop along specific pathways and differentiate into the mature circulating blood cells (Fig. 2)
Summary
Normal adult blood cell production (haematopoiesis) takes place mainly within the bone marrow. It is acknowledged that this microenvironment plays a key role in maintaining the balance between proliferation and differentiation (Morrison and Scadden 2014; Anthony and Link 2014). Specific regions or niches within the marrow are associated with distinct stem cell populations and this in turn is due to the stromal cell populations present and the regulatory molecules which they produce. The earliest stem cells, known as quiescent cells, are generally found at the interface between the bone and bone marrow or endosteal region. Matricellular proteins, including CCN family members, play a key regulatory role in the bone marrow microenvironment (McCallum and Irvine 2009; Cheung et al 2014; Johnson et al 2014a) (Fig. 1)
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