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)

It has been postulated that platelet-derived growth factor and platelet factor 4 (PF4) are involved in the imbalance of the mechanism of medullar stroma maintenance which triggers off the bone marrow myelofibrotic process. In this work we compare the PF4 and the beta-thromboglobulin (beta-TG) and mitogenic activity in platelet-poor plasma (PPP) and platelet extracts (PE) from patients with myeloproliferative disorders (MPD) with those of secondary thrombocytosis (ST) and normal volunteers. Statistically significant differences were found between MPD and ST patients or controls, but none between ST and controls in all the parameters studied. Maximal differences in platelet-derived factors (PDFs) between MPD and control groups were found in polycythemia vera patients. However, the relationship between the presence of myelofibrosis and abnormal levels of beta-TG, PF4 and mitogenic activity in PPP and PE was only observed in patients with agnogenic myeloid metaplasia (AMM). These results show that PDFs are specifically decreased in MPD platelets. Furthermore, no statistical correlation was found between PDFs and the number of platelets. However, other unknown factors or conditions would be necessary to develop myelofibrosis in MPD, which is present in AMM.
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PMID:Abnormal levels of platelet-specific proteins and mitogenic activity in myeloproliferative disease. 138 57

The Philadelphia negative chronic myeloproliferative neoplasms are hematological disorders with several diagnostic challenges. Due to recent molecular findings, the WHO classification of Tumors of Hematopoietic and Lymphoid Tissue 2008 reorganized the field of chronic myeloproliferative diseases. Thus, specific molecular markers provide important information for current diagnostic strategies. This review highlights the important diagnostic tools in classical and atypical myeloproliferative neoplasms mainly the JAK2V617F mutation, the Mpl receptor, Polycythemia rubra vera 1 (PRV1), platelet-derived growth-factor receptor alpha (PDGFRA), platelet-derived growth-factor receptor beta (PDGFRB), fibroblast growth-factor receptor 1 (FGFR1) and c-kit tyrosine kinase. A description of the origin, clinical correlations and role in diagnosis and therapy is provided for each of these molecular markers.
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PMID:Molecular markers guide diagnosis and treatment in Philadelphia chromosome-negative myeloproliferative disorders (Review). 2012 96

Chronic myeloproliferative neoplasms (MPN) are stem cell disorders driven by mutations in JAK2, CALR, or MPL genes and characterized by myeloid proliferation and increased blood cell counts. They encompass three closely related conditions, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Elevated levels of cytokines released by clonal and non-clonal cells generate a chronic proinflammatory state that contributes to disease pathogenesis. Thrombosis represents the most common cause of morbidity and mortality in MPN, although paradoxically, patients may also present with a bleeding diathesis. The mechanisms leading to thrombosis are complex and multiple and include increased blood cells together with qualitative abnormalities of red cells, leukocytes, and platelets that favor a prothrombotic activated phenotype. The functional interplay between blood cells, the clotting cascade, and dysfunctional endothelium contributes to hypercoagulability and this process is perpetuated by the effect of inflammatory cytokines. In addition to their well-known function in hemostasis, platelets contribute to innate immunity and inflammation and play a key role in MPN thromboinflammatory state. In vivo platelet activation leads to platelet aggregate formation and exposure of adhesion molecules which favor their interaction with activated neutrophils and monocytes leading to circulating platelet-leukocyte heterotypic aggregates. Platelets are recruited to the activated endothelium further enhancing the reciprocal activation of both cell types. Crosstalk between activated cells drives cytokine production, further fuelling the self-reinforcing thromboinflammatory loop. In addition, MPN platelets provide a procoagulant scaffold which triggers the coagulation cascade and platelet-derived microparticles amplify this response. Markers of platelet, leukocyte, endothelial and coagulation activation are increased in MPN patients although prospective studies are required to determine the potential value of these parameters for identifying patients at increased thrombotic risk. Thrombosis remains the main complication of MPN patients, with a high risk of recurrence despite adequate cytoreductive and antithrombotic treatment. Deeper insight into the mechanism favoring thrombosis development in this setting may lead to novel therapeutic approaches for MPN thrombosis. Considering the critical role of inflammation in the vascular risk, concomitant targeting of inflammatory pathways could potentially impact on primary or secondary prevention strategies.
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PMID:Platelets as Mediators of Thromboinflammation in Chronic Myeloproliferative Neoplasms. 3125 39