Genetically heterogeneous origins of idiopathic erythrocytosis.
The idiopathic erythrocytosis (IE) group of disorders is defined by an absolute increase in red cell mass and hematocrit without elevation of the megakaryocytic or granulocytic lineages. It is associated with a wide range of serum erythropoietin (Epo) levels and broadly falls into groups of raised/inappropriately normal or low/undetectable Epo levels. A spectrum of molecular defects has been described in association with IE, which reflects the heterogeneity of this disorder. To date the most common identified cause of IE has been mutations in the von Hippel Landau (VHL) protein, which results in aberrant oxygen sensing and dysregulated Epo production. Studying the molecular basis of IE will provide insights into the control of Epo synthesis and Epo-induced signaling pathways.
Percy
M J
MJ
Department of Haematology, Belfast City Hospital, Floor C, Lisburn Road, Belfast, Northern Ireland, UK.
D019281:Dimerization; D004911:Erythrocyte Volume; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D000860:Hypoxia / Q000503:physiopathology; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010100:Oxygen / Q000097:blood; D011086:Polycythemia / Q000235:genetics* / Q000503:physiopathology; D011393:Procollagen-Proline Dioxygenase / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017467:Receptors, Erythropoietin / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000502:physiology
D051793:Hypoxia-Inducible Factor 1; D017467:Receptors, Erythropoietin; D014157:Transcription Factors; D025801:Ubiquitin; D004921:Erythropoietin; D011393:Procollagen-Proline Dioxygenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D011494:Protein Kinases; D046988:Proteasome Endopeptidase Complex; C497446:VHL protein, human; D010100:Oxygen