TAILIEUCHUNG - Chapter 103. Polycythemia 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. Within this broad classification, however, significant phenotypic heterogeneity exists. . | Chapter 103. Polycythemia 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. 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 PDGFRa 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 .

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