Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The myeloproliferative disorders polycythemia vera, essential thrombocytosis, and primary myelofibrosis are clonal disorders arising in a pluripotent hematopoietic stem cell, causing an unregulated increase in the number of erythrocytes, leukocytes, or platelets, alone or in combination; eventual marrow dominance by the progeny of the involved stem cell; and a tendency to arterial or venous thrombosis, marrow fibrosis, splenomegaly, or transformation to acute leukemia, albeit at widely varying frequencies. The discovery of an activating mutation (V617F) in the gene for JAK2 (Janus kinase 2), a tyrosine kinase utilized by hematopoietic cell receptors for erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor, provided an explanation for the shared clinical features of these 3 disorders. Constitutive JAK2 activation provides a growth and survival advantage to the hematopoietic cells of the affected clone. Because signaling by the mutated kinase utilizes normal pathways, the result is overproduction of morphologically normal blood cells, an often indolent course, and (in essential thrombocytosis) usually a normal life span. Because the erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor receptors are all constitutively activated, polycythemia vera is the potential ultimate clinical phenotype of the JAK2 V617F mutation and, as a corollary, is the most common of the 3 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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PMID:Narrative review: Thrombocytosis, polycythemia vera, and JAK2 mutations: The phenotypic mimicry of chronic myeloproliferation. 2019 36

Polycythemia vera (PV) is relatively uncommon in early adulthood, and evidence about the prevalence of the Janus kinase 2 (JAK2) V617F mutation in the general population is limited. Here, we report a previously healthy volunteer peripheral blood stem cell (PBSC) donor who developed symptomatic PV with the JAK2 V617F mutation 2 years after PBSC mobilization and harvest. The characteristic mutation was identified retrospectively in the blood sample of the donor at the confirmation typing stage, which was before granulocyte colony-stimulating factor injection. This report presents a safety issue for both donor and recipient of hematopoietic stem cell transplantation. Clinicians should be aware of this during health workup and postdonation follow-up of unrelated PBSC donors. Any abnormal and/or equivocal laboratory data, especially during the donor workup stage, should not be overlooked.
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PMID:Janus kinase 2 V617F mutation in an unrelated peripheral blood stem cell donor. 3069 34


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