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INTRODUCTION

The World Health Organization (WHO) classification of the chronic myeloproliferative neoplasms (MPNs) includes eight disorders, some of which are rare or poorly characterized (Table 99-1) but all of which share an origin in a hematopoietic cell; overproduction of one or more of the formed elements of the blood without significant dysplasia; and 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, whereas in other diseases, 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.

TABLE 99-1World Health Organization Classification of Chronic Myeloproliferative Neoplasms

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, PV, PMF, and ET are characterized by driver mutations that directly or indirectly constitutively activate JAK2, a tyrosine kinase essential for the function of the erythropoietin and thrombopoietin receptors and also utilized by the granulocyte colony-stimulating factor receptor. This important distinction is reflected in the natural histories of CML, CNL, and CEL, which are usually measured in years, with a high rate of leukemic transformation. The natural histories of PV, PMF, and ET, by contrast, are usually measured in decades, and transformation to acute leukemia is uncommon in the absence of chemotherapy. This chapter focuses only on PV, PMF, and ET because their clinical features and driver mutation overlap are substantial, though their disease duration varies.

The other chronic MPNs will be discussed in Chaps. 101 and 106.

POLYCYTHEMIA VERA

PV is a clonal hematopoietic stem cell disorder in which phenotypically normal red cells, granulocytes, and platelets accumulate in the absence of a recognizable physiologic stimulus. The most common of the MPN, PV occurs in 2.5 per 100,000 persons, sparing no adult age group and increasing with age to rates over 10/100,000. Familial transmission is infrequent, and women predominate among sporadic cases.

ETIOLOGY

Image not available. Nonrandom chromosome abnormalities such as deletion 20q and deletion 13q or trisomy 9 occur in up to 30% of untreated PV patients, but unlike CML, no consistent cytogenetic abnormality has been associated with the disorder. However, a mutation in ...

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