Essential Thrombocythemia & Polycythemia Vera -Part of spectrum of Myeloproliferative disorders (ET, PV, CML, and Myelofibrosis, chronic

neutrophilic leukemia, chronic eosinophilic leukemia )defined by WHO -ET and PV are defined by their sensitivity to their own growth factors, Tpo for ET and Epo for PV -erythroid precursors in PV and megakaryocyte precursors in ET -negative feedback mechanism in PV with respect to renal EPO production -however in ET, there really Is no negative feedback, there are elevated or inappropriate levels of Tpo when there is thrombocytosis -this may be due to a defect in expression or down regulation of Tpo-R -free Tpo levels are modulated by its binding to its receptors -there is also hypersensitivity of megakaryocytes to the action of the hormone -

-JAK-STAT is a key signal transduction, part of cascade as soon as growth factor binds to its receptors, JAK2 Mutation status helps further include PV or ET in the differential diagnosis for a certain progenitor hyperplasia. JAK2 can actually protect Tpo-R from proteasome degradation. -Clinical implications: bleeding, thrombotic, and vascular complications are important things to consider with respect to PV and ET -Leukocytosis : leukocytes are affected by the hyperplasia of bone marrow cells, PMN activation has been reported in both PV and ET. Interestingly enough, leukocytosis is being looked at as additional risk factor for developing thrombotic complications in these disorders.

Essential Thrombocythemia

Polycythemia Vera