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The World Health Organization (WHO) classification of the chronic myeloproliferative diseases (MPDs) includes eight disorders, some of which are rare or poorly characterized (Table 13-1) but all of which share an origin in a multipotent hematopoietic progenitor cell; overproduction of one or more of the formed elements of the blood without significant dysplasia; a predilection to extramedullary hematopoiesis, myelofibrosis; and transformation at varying rates to acute leukemia. Within this broad classification, however, significant phenotypic heterogeneity exists. Some diseases such as chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), and chronic eosinophilic leukemia (CEL) express primarily a myeloid phenotype, while in others such as polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocytosis (ET), erythroid or megakaryocytic hyperplasia predominates. The latter three disorders, in contrast to the former three, also appear capable of transforming into each other.
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Such phenotypic heterogeneity has a genetic basis; CML is the consequence of the balanced translocation between chromosomes 9 and 22 (t[9;22][q34;11]), CNL has been associated with a t(15;19) translocation, and CEL occurs with a deletion or balanced translocations involving the PDGFRα gene. By contrast, to a greater or lesser extent, PV, PMF, and ET are characterized by expression of a JAK2 mutation, V617F that causes constitutive activation of this tyrosine kinase that is essential for the function of the erythropoietin and thrombopoietin receptors but not the granulocyte colony-stimulating factor receptor. This essential distinction is also reflected in the natural history of CML, CNL, and CEL, which is usually measured in years, and their high rate of transformation into acute leukemia. By contrast, the natural history of PV, PMF, and ET is usually measured in decades, and transformation to acute leukemia is uncommon in the absence of exposure to mutagenic agents. This chapter, therefore, will focus only on PV, PMF, and ET because their clinical overlap is substantial but their clinical courses are distinctly different. Other chronic myeloproliferative disorders will be discussed in Chap. 14.
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PV is a clonal disorder involving a multipotent hematopoietic progenitor cell in which phenotypically normal red cells, granulocytes, and platelets accumulate in the absence of a recognizable physiologic stimulus. The most common of the chronic myeloproliferative disorders, PV occurs in 2 per 100,000 persons, sparing no adult age group and increasing with age to rates as high as 18/100,000. Familial transmission occurs but is infrequent and women predominate among sporadic cases.
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The etiology of PV is unknown. Although nonrandom chromosome abnormalities such as 20q and trisomy 8 and 9 have been documented ...