What is the possible pathogenesis of polycythemia vera?

Expert Solution

Polycythemia vera is characterized by increased marrow production of red cells, granulocytes and platelets ( panmyelosis) but it is the increase in red cells (polycythemia) that is responsible for most of the clinical symptoms.

JAK2 participates in the JAK/STAT pathway which lies downstream of multiple hematopoietic growth factor receptors, including the erythropoietin receptor. In polycythemia vera, the progenitor cells undergo transformation which make progenitor cells to require very less amount of erythropoietin and other growth factors due to constitutive JAK2 signalling. Therefore serum erythropoietin levels are low. Polycythemia leads to increased haematocrit which further leads to increased blood viscosity. This factors along with thrombocytosis and abnormal platelet function make the patient prone for bleeding and thrombosis.

The JAK2 undergoes a point mutation at residue number 617 which substitute valine to phenylalanine in almost all of the patients. This mutation renders hematopoietic cell lines growth factor independent and cause polycythemia vera syndrome.

gladiator answered 1 year ago

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