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

Harrisons Internal Medicine Chapter 103. Polycythemia Vera and Other Myeloproliferative DiseasesPolycythemia IntroductionVeraandOtherMyeloproliferativeDiseases: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) Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 1) Harrisons Internal Medicine > Chapter 103. Polycythemia Vera andOther Myeloproliferative Diseases Polycythemia Vera and Other Myeloproliferative Diseases:Introduction The World Health Organization (WHO) classification of the chronicmyeloproliferative diseases includes seven disorders, some of which are rare orpoorly characterized (Table 103-1) but all of which share an origin in amultipotent hematopoietic progenitor cell, overproduction of one or more of theformed elements of the blood without significant dysplasia, a predilection toextramedullary hematopoiesis, myelofibrosis, and transformation at varying ratesto acute leukemia. Within this broad classification, however, significant phenotypicheterogeneity 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 aspolycythemia vera (PV), idiopathic myelofibrosis (IMF), and essentialthrombocytosis (ET), erythroid or megakaryocytic hyperplasia predominates. Thelatter three disorders, in contrast to the former three, also appear capable oftransforming into each other. Table 103-1 WHO Classification of Chronic MyeloproliferativeDisorders 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 consequenceof 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 orbalanced translocations involving the PDGFRα gene. By contrast, to a greater or lesser extent, PV, IMF, and ET are characterizedby expression of a JAK2 mutation, V617F, which causes constitutive activation ofthis tyrosine kinase that is essential for the function of the erythropoietin andthrombopoietin receptors but not the granulocyte colony–stimulating factorreceptor. 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 oftransformation into acute leukemia. By contrast, the natural history of PV, IMF,and ET is usually measured in decades, and transformation to acute leukemia isuncommon in the absence of exposure to mutagenic agents. This chapter, therefore, will focus only on PV, IMF, and ET, because theirclinical 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 multipotenthematopoietic progenitor cell in which phenotypically normal red cells,granulocytes, and platelets accumulate in the absence of a recognizablephysiologic stimulus. The most common of the chronic myeloproliferative disorders, PV occursin 2 per 100,000 persons, sparing no adult age group and increasing with age torates as high as 18/100,000. Familial transmission occurs but is infrequent. Aslight overall male predominance has been observed, but women predominatewithin the reproductive age range.