SPPS249Epo033011-bw

SPPS249Epo033011-bw - John W. Adamson, M.D. Division of...

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John W. Adamson, M.D. Division of Hematology/Oncology Historical Milestones
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Erythropoietin 1836 – Bright describes anemia as a complication of renal failure 1863 – Jourdanet describes hypoxic polycythemia in inhabitants of Mexican mountains Erythropoietin 1906 – Carnot and DeFlandre postulate the existence of a hormone responsible for erythropoiesis 1953 – Erslev identi±es an erythropoietic stimulating activity in the plasma of anemic rabbits 1957 – Jacobson, Goldwasser, Fried and Plzak establish that the kidney produces ‘erythropoietin’
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Erythropoietin 1977 – Miyake, Kung and Goldwasser purify human erythropoietin 1983 – Lin et al. Isolate and clone the human erythropoietin gene 1985 – The Frst clinical trials of recombinant human erythropoietin begin at the University of Washington and the Northwest Kidney Centers in Seattle. 1989 -±‐ EPOGEN ® (epoetin alfa) is the Frst recombinant human erythropoietin approved by the ²DA for sale in the U.S. What is Erythropoietin? A glycoprotein of 64,000 molecular weight Made up of 165 amino acids 40% of its mass is carbohydrate Essential for the production of red blood cells
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Where Does Erythropoietin Come From and What Does It Do? Made in the kidney (>95%) and liver (<5%) Produced by peritubular capillary lining cells in the renal cortex Production is inversely related to tissue oxygenation Circulates in the plasma and acts on progenitor cells in the bone marrow via specifc erythropoietin receptors (EpoR)
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Regulation of Erythropoietin Gene Expression
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Signaling through the Erythropoietin Receptor Erythropoietin Through its interactions with EpoR: Maintains, expands and causes terminal maturation of erythroid progenitor cells – at least in part by preventing ‘programmed cell death’ (apoptosis) Causes premature release of marrow reticulocytes
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Distribution of “EpoR” Erythroid progenitor cells
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SPPS249Epo033011-bw - John W. Adamson, M.D. Division of...

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