Essential thrombocythemia: a review of the clinical features, diagnostic challenges, and treatment modalities in the era of molecular discovery

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm that is associated with diminished quality of life, thrombohemorrhagic complications, and transformation to myelofibrosis (MF) and acute leukemia (AML). The important recent discoveries of driver mutations, including the calreticulin gene in addition to JAK2 and MPL, have led to a greater understanding of disease pathogenesis and set the stage for the advent of more sophisticated prognostic, diagnostic, and therapeutic strategies. In this paper we summarize recent studies describing the molecular basis of ET. We review the prognostic importance of establishing a ‘true’ ET diagnosis, as well as risk factors for the development of adverse outcomes including thrombosis, AML (2% risk at 15 years), and MF (9% risk at 15 years). Finally, we discuss the decision to initiate treatment and assess the quality of evidence supporting the use of established, available therapies as well as novel treatments. Special situations, such as pregnancy, familial ET, and extreme thrombocytosis will also be discussed.