Abnormalities of cytokine receptor signalling contributing to diseases of red blood cell production

The production of erythroid cells is a dynamic and exquisitely regulated pr ocess. The mature red cell is only the final phase of a complex but orderly series of genetic events that are initiated at the time a multipotent stem cell becomes committed to expressing the erythroid programme. Aberrations either in the intrinsic generation and/or amplification of functional eryth roid cells or in the regulatory influences of microenvironment or cytokines form the basis for a number of blood diseases. In this review we focus upo n abnormalities in red blood cell production and discuss how alterations in cytokine regulation of red blood cell production may contribute to these d isease processes. We discuss clinical states in which blood red cell number s are altered, including primary familial and congenital polycythaemia, the myeloproliferative disorder polycythaemia vera, erythroleukaemia, and Diam ond-Blackfan anaemia. These disorders are briefly described and evidence su pporting a potential role of specific cytokine receptor signalling defects as contributing to these phenotypes is discussed.