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)

Polycythemia vera (PV), an acquired, chronic, clonal disorder arising in a multipotential hematopoietic progenitor cell, is characterized by hyperplasia of three major myeloid lineages, with a pronounced increase in cells of the erythroid lineage. Erythroid progenitor cells in PV are strikingly hypersensitive to insulin-like growth factor-I (IGF-I); this effect is specific and is mediated through the IGF-I receptor. To investigate the possibility that in PV the increase in number of erythroid progenitors and their hypersensitivity to IGF-I result from a defect in negative regulation of cytokine activity, we examined the expression of members of the SOCS gene family. Circulating mononuclear cells, grown in serum-free methylcellulose medium in the presence of IGF-I, produced BFU-E-derived colonies whose cells revealed a reduction of SOCS-2 and SOCS-3 expression in PV only. Overexpression of these genes in transfected PV cells reduced their erythroid overgrowth and IGF-I hypersensitivity. We hypothesize that a defect in expression of SOCS-2 and SOCS-3 genes may be crucial for the IGF-I hypersensitivity and progressive increase in erythroid cell population size characteristic of PV.
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PMID:Overexpression of SOCS-2 and SOCS-3 genes reverses erythroid overgrowth and IGF-I hypersensitivity of primary polycythemia vera (PV) cells. 1732 42

Dysregulated signaling is a hallmark of chronic myeloproliferative neoplasms (MPNs), as evidenced by the identification of the activating JAK2 V617F somatic mutation in almost all patients with polycythemia vera (PV) and 50-60% of essential thrombocythemia and primary myelofibrosis patients. These disorders are clinically distinct, raising the question of how a single mutation can result in such phenotypic diversity. Mouse models have demonstrated that the level of JAK2 V617F expression can modulate the phenotype, and clinical studies of JAK2 V617F allele burden have reported similar findings. It has also been hypothesized that one or more pre-JAK2 V617F events may modify the MPN phenotype. However, the molecular basis of JAK2 V617F-negative essential thrombocythemia and primary myelofibrosis remains largely unexplained. Mutations in the TET2 gene have been identified in both JAK2 V617F-positive and -negative MPNs and other myeloid neoplasms, but their functional and clinical significance have yet to be clarified. In addition, recent reports have identified a specific germline haplotype that increases the predisposition to MPNs. The role of inhibitory pathways (e.g., SOCS and LNK) in regulating JAK-STAT signaling in MPNs is being increasingly recognized. The implications of these findings and their clinical relevance are the focus of this article.
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PMID:JAK2 V617F and beyond: role of genetics and aberrant signaling in the pathogenesis of myeloproliferative neoplasms. 2108 83

In this study we investigated whether neoplastic transformation occurring in Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs) could involve also the endothelial cell compartment. We evaluated the level of endothelial colony-forming cells (E-CFCs) in 42 patients (15 with polycythemia vera, 12 with essential thrombocythemia, and 15 with primary myelofibrosis). All patients had 1 molecular abnormality (JAK2(V617F) or MPL(W515K) mutations, SOCS gene hypermethylation, clonal pattern of growth) detectable in their granulocytes. The growth of colonies was obtained in 22 patients and, among them, patients with primary myelofibrosis exhibited the highest level of E-CFCs. We found that E-CFCs exhibited no molecular abnormalities in12 patients, had SOCS gene hypermethylation, were polyclonal at human androgen receptor analysis in 5 patients, and resulted in JAK2(V617F) mutated and clonal in 5 additional patients, all experiencing thrombotic complications. On the whole, patients with altered E-CFCs required antiproliferative therapy more frequently than patients with normal E-CFCs. Moreover JAK2(V617F)-positive E-CFCs showed signal transducer and activator of transcription 5 and 3 phosphorylation rates higher than E-CFCs isolated from healthy persons and patients with MPN without molecular abnormalities. Finally, JAK2(V617F)-positive E-CFCs exhibited a high proficiency to adhere to normal mononuclear cells. This study highlights a novel mechanism underlying the thrombophilia observed in MPN.
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PMID:Endothelial progenitor cells are clonal and exhibit the JAK2(V617F) mutation in a subset of thrombotic patients with Ph-negative myeloproliferative neoplasms. 2121 85