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INTRODUCTION

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SUMMARY

Essential thrombocythemia is a clonal stem cell disorder characterized by an overproduction of platelets and associated with mutations in the JAK2, CALR, or MPL gene. Complications include thrombosis (predominantly arterial), hemorrhage, and progression to myelofibrosis or acute myeloid leukemia. Diagnosis requires exclusion of reactive thrombocytosis and other myeloid malignancies associated with a raised platelet count. Therapy is aimed at reducing thrombotic complications and includes modification of known cardiovascular risk factors and antiplatelet therapy for the majority of patients. Those at high risk of thrombosis are also considered for cytoreductive therapy with agents such as hydroxyurea, anagrelide or interferon-α. Although the majority of patients can expect to live for many years, mortality rates are increased compared to the general population as a consequence of disease complications.

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DEFINITION AND HISTORY

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Essential thrombocythemia (ET), one of the myeloproliferative neoplasms (MPNs), is a clonal hematopoietic stem cell disorder characterized by thrombocytosis and associated with thrombotic and hemorrhagic complications. First recognized as a specific disease entity in 19341 and as a clonal disorder in 1981,2 ET shares clinical and pathologic similarities with other MPNs, particularly polycythemia vera (PV) and primary myelofibrosis (PMF).

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EPIDEMIOLOGY

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The annual incidence of ET is in the order of 1 to 2.5 per 100,000 per population and appears slightly more common in females.3,4 Patients may present at any age, although ET is largely a disorder of later life with a peak incidence between the ages of 50 and 70 years. Presentation in childhood is rare but well recognized.

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ETIOLOGY

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Little is known about the precise etiology of this disorder, although environmental factors such as exposure to radiation have been implicated in the genesis of other MPNs.5 Both registry data and kindred studies suggest a familial tendency to develop MPNs, including ET.6,7 This predisposition appears to be explained in part by inheritance of a specific haplotype that contains the Janus family of tyrosine kinases type 2 (JAK2) gene.8

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Acronyms and Abbreviations:

AML, acute myeloid leukemia; CALR, calreticulin gene; CML, chronic myeloid leukemia; ET, essential thrombocythemia; JAK2, Janus family of tyrosine kinases type 2; MPL, the thrombopoietin receptor; MPN, myeloproliferative neoplasm; PCR, polymerase chain reaction; PMF, primary myelofibrosis; PV, polycythemia vera; RARS-T, refractory anemia with ringed sideroblasts and thrombocytosis; STAT, signal transducer and activator of transcription.

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PATHOGENESIS

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ET is characterized by hyperactive cytokine signaling which in 50 to 60 percent of cases is the result of somatic mutations targeting components of signaling pathways, including the JAK2 gene or the thrombopoietin receptor gene (MPL). Mutations in calreticulin gene (CALR) are present in the majority of JAK2/MPL–wild-type patients, leaving approximately 10 percent of ET patients without a mutation in any of these genes (JAK2/MPL/CALR–wild-type or “triple-negative” patients). ...

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