Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 1)

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Harrison's Internal Medicine Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases Polycythemia Introduction Vera and Other Myeloproliferative Diseases: The World Health Organization (WHO) classification of the chronic myeloproliferative diseases includes seven disorders, some of which are rare or poorly characterized (Table 103-1) 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. ...

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Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 1) Harrison's Internal Medicine > Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases Polycythemia Vera and Other Myeloproliferative Diseases: Introduction The World Health Organization (WHO) classification of the chronic myeloproliferative diseases includes seven disorders, some of which are rare or poorly characterized (Table 103-1) 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 myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL) and chronic eosinophilic leukemia (CEL) express primarily a myeloid phenotype, while in others, such as polycythemia vera (PV), idiopathic myelofibrosis (IMF), 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. Table 103-1 WHO Classification of Chronic Myeloproliferative Disorders Chronic myelogenous leukemia, [Ph chromosome t(9;22)(q34;11), BCR/ABL-positive] Chronic neutrophilic leukemia Chronic eosinophilic leukemia (and the hypereosinophilic syndrome)
Polycythemia vera Chronic idiopathic myelofibrosis (with extramedullary hematopoiesis) Essential thrombocythemia Chronic myeloproliferative disease, unclassifiable This 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 with a deletion or balanced translocations involving the PDGFRα gene. By contrast, to a greater or lesser extent, PV, IMF, and ET are characterized by expression of a JAK2 mutation, V617F, which 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, IMF, 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, IMF, and ET, because their clinical overlap is substantial and their clinical courses are distinctly different. Other chronic myeloproliferative disorders will be discussed in Chapter 104. Polycythemia Vera Polycythemia vera (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. A slight overall male predominance has been observed, but women predominate within the reproductive age range.