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

Agnogenic myeloid metaplasia (AMM) is characterized by bone marrow fibrosis with abnormal accumulation of extracellular matrix components (ECM), which is dependent on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Twenty-five patients with AMM, 30 with essential thrombocythemia (ET), 12 with polycythemia vera (PV) and 20 normal control subjects were studied. AMM patients had decreased plasma levels of MMP-3 and marked elevated levels of TIMP-1, but MMP-1, MMP-2 and MMP-9 levels were not significantly different from control subjects. Elevated levels of plasma TIMP-1, but not MMPs, were found in ET and PV. Reduced MMP activity together with increased TIMP-1 activity may be essential in fibrosis formation.
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PMID:Plasma matrix metalloproteinase and tissue inhibitor of metalloproteinase in patients with agnogenic myeloid metaplasia or idiopathic primary myelofibrosis. 1243 48

In order to investigate the biologic processes underlying and resulting from the megakaryocytic hyperplasia that characterizes idiopathic myelofibrosis (IMF), peripheral blood CD34+ cells isolated from patients with IMF, polycythemia vera (PV), and G-CSF-mobilized healthy volunteers were cultured in the presence of stem cell factor and thrombopoietin. IMF CD34+ cells generated 24-fold greater numbers of megakaryocytes (MKs) than normal CD34+ cells. IMF MKs were also shown to have a delayed pattern of apoptosis and to overexpress the antiapoptotic protein bcl-xL. MK hyperplasia in IMF is, therefore, likely a consequence of both the increased ability of IMF progenitor cells to generate MKs and a decreased rate of MK apoptosis. Media conditioned (CM) by CD61+ cells generated in vitro from CD34+ cells were then assayed for the levels of growth factors and proteases. Higher levels of transforming growth factor-beta (TGF-beta) and active matrix metalloproteinase-9 (MMP9) were observed in media conditioned with IMF CD61+ cells than normal or PV CD61+ cells. Both normal and IMF CD61+ cells produced similar levels of VEGF. MK-derived TGF-B and MMP-9, therefore, likely contribute to the development of many pathological epiphenomena associated with IMF.
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PMID:Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. 1791 55

Primary myelofibrosis (PMF) and polycythemia vera (PV) are chronic myeloproliferative neoplasms. PMF and, to a lesser degree, PV are characterized by constitutive mobilization of hematopoietic stem cells (HSC) and progenitor cells (HPC) into the peripheral blood (PB). The interaction between the chemokine CXCL12 and its receptor CXCR4 plays a pivotal role in determining the trafficking of CD34(+) cells between the bone marrow (BM) and the PB. PMF, but not PV, is associated with downregulation of CXCR4 by CD34(+) cells due to epigenetic events. Both PV and PMF patients have elevated levels of immunoreactive forms of CXCL12 in the BM and PB. Using electrospray mass spectrometry, the PB and BM plasma of PV and PMF patients was shown to contain reduced amounts of intact CXCL12 but significant amounts of several truncated forms of CXCL12, which are lacking in normal PB and BM plasma. These truncated forms of CXCL12 are the product of the action of several serine proteases, including dipeptidyl peptidase-IV, neutrophil elastase, matrix metalloproteinase-2 (MMP-2), MMP-9, and cathepsin G. Unlike CXCL12, these truncates either lack the ability to act as a chemoattractant for CD34(+) cells and/or act as an antagonist to the action of CXCL12. These data suggest that proteolytic degradation of CXCL12 is characteristic of both PV and PMF and that the resulting truncated forms of CXCL12, in addition to the reduced expression of CXCR4 by CD34(+) cells, lead to a profound mobilization of HSC/HPC in PMF.
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PMID:The effect of CXCL12 processing on CD34+ cell migration in myeloproliferative neoplasms. 2038 88

Neutrophil gelatinaase-associated lipocalin (NGAL) is a glycoprotein bound with matrix metalloproteinase-9 (MMP-9) in human neutrophils, and elevated tissue NGAL expression has been documented in different infectious and inflammatory conditions. Recent evidence suggests that NGAL expression is induced in many types of human cancer. Moreover, NGAL is required for BCR-ABL-induced tumorigenesis. The aim of the present study was to measure serum levels of NGAL in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We also evaluated NGAL levels in patients with ET and PV with and without thrombotic events, to explore a possible correlation of NGAL with platelet and leukocyte activation, and in patients with sepsis. Serum NGAL levels in the study population were significantly higher than in healthy adults and in subjects with sepsis. A correlation between NGAL and the number of white cells and neutrophils was found in patients with PV and ET. NGAL serum levels were not different depending on the presence or not of the JAK2 mutation, and a mutant allele dosage effect was not observed for NGAL levels. Patients with PV and ET with thrombosis did not have significantly higher levels of NGAL. We were unable to demonstrate a significant association between serum NGAL levels and CD11b or CD62 expression. In conclusion, our study reports evidence demonstrating that increased levels of NGAL appear to be a characteristic of patients with PV and ET.
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PMID:Increased serum levels of neutrophil gelatinase-associated lipocalin in patients with essential thrombocythemia and polycythemia vera. 2226 71