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Physiology in Medicine review article. Clonal disorders arise in a pluripotent hematopoietic stem cell, causing an unregulated increase in the number of erythrocytes, leukocytes, or platelets, alone or in combination. The discovery of an activating mutation (V617F) in the gene for JAK2 (Janus kinase 2) provides an explanation for the shared clinical features of these three disorders. The number of cells expressing the JAK2 V617F mutation (the allele burden) seems to correlate with the clinical phenotype. Preliminary results of clinical trials with agents that inhibit the mutated kinase indicate a reduction in splenomegaly and alleviation of night sweats, fatigue, and pruritus.
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