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Polycythemia vera is a disorder in the group of chronic myeloproliferative disorders (MPDs), also refered to as myeloproliferative neoplasms, that includes essential thrombocythemia (ET), primary myelofibrosis (PMF), and chronic myelogenous leukemia (CML). Polycythemia vera is an acquired clonal primary polycythemic disorder. Primary polycythemias result from abnormal intrinsic properties of erythroid progenitors that proliferate independently or excessively in response to extrinsic regulators; low serum erythropoietin is their hallmark. The most common primary polycythemia is polycythemia vera. Polycythemia vera arises from mutations in a multipotential hematopoietic stem cell, which results in an excess production of functionally normal erythrocytes, a variable overproduction of granulocytes and monocytes, and of platelets. It is usually accompanied by splenomegaly. Most patients with polycythemia vera have a somatic mutations of the Janus-type tyrosine kinase-2 gene (JAK2) that is detectable in blood myeloid cells. This mutation, JAK2 V617F, results in constitutive hyperactivity of JAK2 stemming from the loss-of-function of its negative regulatory domain. JAK2 V617F is present in virtually all cases of polycythemia vera; however, ET, MF, and, much less commonly, other hematologic neoplastic disorders are also associated with this mutation, albeit at lower frequency. As with other clonal hematologic disorders, polycythemia vera can undergo a clonal evolution to PMF (typically JAK2 V617-positive) and acute leukemia (often JAK2 V617-negative). In virtually all PV JAK2 V617F-positive patients at least some progenitors exist that became homozygous for the JAK2 V617F mutation by uniparenteral disomy acquired by mitotic recombination and the majority of these account for the erythropoietin-independent erythroid colonies detected in vitro by clonogenic burst-forming unit–erythroid assay (BFU-E). The JAK2 V617F mutation is not a cause of clonal proliferation of these disorders but is preceded by other germ-line and somatic mutation(s) that remain to be identified. Arterial and venous thromboses are the major causes of morbidity and mortality of polycythemia vera. A small proportion of patients develop secondary myelofibrosis (spent phase) and/or an invariably fatal acute leukemic transformation. Myelosuppressive therapy has been an effective mode of therapy, with drugs such as hydroxyurea, busulfan, and radioactive phosphorus useful in controlling proliferation of all blood cell lineages. Myelosuppressive therapy decreases the incidence of thrombotic complications but these drugs have variable leukemogenic potential. Newer, better-tolerated preparations of interferon such as pegylated interferon-α may lead to complete hematologic remission and restoration of polyclonal hematopoiesis. Targeted therapy with JAK2 kinase inhibitors is currently being evaluated for effects on splenomegaly and splenomegaly-associated symptoms, hypercoagulability, and control of the polycythemia vera clone.

Acronyms and Abbreviations

Acronyms and abbreviations used in this chapter include: bcl-x, an antiapoptotic protein; BFU-E, burst-forming unit–erythroid; EEC, endogenous erythroid colonies; EPO, erythropoietin; ET, essential thrombocytosis; c-MPL, thrombopoietin receptor; JAK2, Janus-type tyrosine kinase 2; MPDs, myeloproliferative disorders; PFCP, primary familial and congenital polycythemia; PMF, primary myelofibrosis; PV, polycythemia vera; PRV-1, a receptor named polycythemia rubra vera 1.

The term polycythemia, denoting an increased amount of blood, has traditionally been applied to those conditions in which the mass of ...

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