Polycythaemia Essay

787 words - 4 pages

Polycythaemia is a blood disorder defined as an increase in blood erythrocyte concentration. Absolute polycythaemia is where this increase is caused by greater erythrocyte production, determined by measuring the haematocrit level, with one study showing that 83% of sufferors have a haematocrit level of >55%. This should not be confused with relative polycythaemia, caused by a decrease in blood plasma volume often secondary to hypertension. Interestingly, those affected tend to also have increased blood platelet and white cell concentrations, which correlates well with the notion that the disease is caused by a genetic defect in the haematopoietic stem cell population within the bone marrow. ...view middle of the document...

Primary polycythaemia is caused by mutations in proteins within the haematopoietic cells themselves and not a defect of erythropoietin secretion – we know this because sufferors tend to have a low erythropoietin concentration in their blood. A recent study showed that 97% of the primary polycythaemia sufferors tested had the V617F mutation in the JAK2 gene (located in 9p24 from bp 4,985,244 to 5,129,947) with a further 3% having a mutation in JAK2 at a different locus. The protein transcribed by JAK2 stimulates cell hypertrophy and hyperplasia, with the greatest effect in haematopoietic stem cells. The new, mutated protein is overractive causing increased haematopoiesis. The method of action of the JAK2 protein is through the JAK/STAT pathway – two complimentary STAT proteins are usually inactive, but when the JAK2 protein binds to the cytokine receptor, they migrate towards the receptor, bind to it and are phosphorylated. This causes the STAT proteins to dimerise and then travel to the nucleus where they activate the transcription of certain proteins associated with inducing growth and proliferation. Furthermore, a different study showed a 16% prevalence of another mutation to a gene called the TET2 gene (located at 4q24 from base pairs 105,145,874 to 105,279,802) to a sample population of primary polycythaemia sufferors. Currently the function of the TET2 protein is unknown, but if its function is similar to proteins of similar structure it could be...

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