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Advances in understanding the pathogenesis of primary familial and congenital polycythaemia
Author(s) -
Huang Lily J.,
Shen YuMin,
Bulut Gamze B.
Publication year - 2010
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.08069.x
Subject(s) - erythropoietin receptor , erythropoietin , polycythaemia , pathogenesis , context (archaeology) , erythropoiesis , internalization , mechanism (biology) , biology , medicine , immunology , receptor , cancer research , genetics , anemia , paleontology , philosophy , epistemology
Summary Primary familial and congenital polycythemia (PFCP) is an autosomal‐dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid progenitors to erythropoietin (Epo). Several lines of evidence suggest a causal role of truncated erythropoietin receptor (EpoR) in this disease. In this review, we discuss PFCP in the context of erythrocytosis and EpoR signalling. We focus on recent studies describing mechanisms underlying Epo‐dependent EpoR down‐regulation. One mechanism depends on internalization mediated through the p85 regulatory subunit of the Phosphoinositide 3‐Kinase, and the other utilizes ubiquitin‐based proteasomal degradation. Truncated PFCP EpoRs are not properly down‐regulated upon stimulation, underscoring the importance of these mechanisms in the pathogenesis of PFCP.