Lessons to better understanding of hypoxia sensing. Acquired and congenital mutations resulting in polycythemia

Adaptation of the organism to hypoxia has profound effect on multiple tissues including regulation of erythropoiesis, vasculogenesis, a proper regulation of embryogenesis as well as other functions. The elucidation of those congenital or acquired mutations giving rise to disease states affecting physiological systems devoted to oxygen homeostasis provides not only a practical diagnostic and potential therapeutic target, but also allows to identify the essential, non-redundant physiological pathways that may be hitherto unknown. The erythropoietin gene was the first gene expression found to be upregulated by hypoxia; the mechanism of this regulation lead to our current understanding of hypoxia sensing. Thus it is appropriate that the disorders resulting from augmented erythropoiesis are subject of this review.