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)

Among the chronic myeloproliferative disorders, polycythemia vera and essential thrombocythemia are unique because of their association with thrombohemorrhagic manifestations and their relatively indolent clinical course. Patients with essential thrombocythemia may not have a significant shortening of life-expectancy and most may not require specific therapy. However, patients with polycythemia vera have a significant risk of transformation of polycythemia vera into acute leukemia or postpolycythemic myelofibrosis (or both). 'High-risk-for-thrombosis' patients with either polycythemia vera or essential thrombocythemia require specific therapy with a platelet-lowering agent to prevent thrombotic complications. Currently, the standard agent used for this is hydroxyurea. However, its tetratogenic and leukemogenic potential has been of concern. As a result, new platelet-lowering agents are being evaluated in the treatment of polycythemia vera and essential thrombocythemia. Anagrelide and interferon alfa are two such agents and have been shown to be effective in reducing platelet counts in patients with chronic myeloproliferative disorders. The putative mechanism of action of these drugs, their specific activity in polycythemia vera and essential thrombocythemia, side-effect profile, and current indications are discussed herein.
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PMID:New drugs in essential thrombocythemia and polycythemia vera. 921 1

In addition to the criteria of the Polycythemia Vera Study Group, positive markers for essential thrombocythemia (ET) include spontaneous BFU-E, splenomegaly, and megakaryocyte morphology in bone marrow smears and biopsy material. The hematologic features of 11 reported cases of ET in childhood showed platelet counts in excess of 1000 x 10(9)/L in all, slight leukocytosis in 8, and splenomegaly in 9. The presenting thrombohemorrhagic manifestations in 8 symptomatic cases were microcirculatory disturbances and transient neurologic ischemic attacks in 2, recurrent mucocutaneous bleedings in 6, and priapism in 1. There are no reports of ET in childhood complicated by microcirculatory disturbances at platelet counts below 1000 x 10(9)/L. Anagrelide and alpha-interferon, which are non-leukemogenic agents for the reduction of platelet counts, may become the treatment of choice in childhood ET. Anagrelide is tolerated better than alpha-interferon. The potential leukemogenic drugs hydroxyurea and busulfan should be used cautiously and withheld as long as possible.
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PMID:Essential thrombocythemia in childhood. 925 10

Myelodysplasia and the myeloproliferative disorders are clonal hematopoietic stem cell disorders with heterogeneous clinical presentations and prognoses. This review highlights some of the recent progress that has been made in these disorders. Specifically, a number of studies have enhanced our understanding of the pathogenesis of these disorders, and potentially useful animal models for primary myelofibrosis have been developed. New, clinically useful prognostic scoring systems have been devised for myelodysplasia and for primary myelofibrosis. New chemotherapeutic approaches and nonmyelosuppressive alternative therapies for myelodysplasia have been studied. Data on the use of interferon for polycythemia vera and the potential leukemogenesis of hydroxyurea have recently become available. Finally, continued progress has been made in the use of allogeneic (related and unrelated donor) and autologous stem cell transplantation for myelodysplasia.
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PMID:Myelodysplasia and myeloproliferative disorders. 926 54

Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic clonal myeloid disorders that originate from the multipotential hematopoietic stem cell. They are characterized, respectively, by excessive thrombocytosis and erythrocytosis, a high incidence of thrombohemorrhagic events, vasomotor symptoms, and an inherent tendency to undergo leukemic transformation. Current standard therapies to control the excess accumulation of myeloid cells and to provide symptomatic relief carry either a persistent risk of thrombosis, as in the case of phlebotomy, or, in the case of hydroxyurea, the potential for inducing leukemia. None alter the natural history of these diseases. Interferon-alpha has been shown to have potent antiproliferative effects on the hematopoietic stem cells and bone marrow fibroblasts and, as a result, has received much attention as a therapeutic agent for chronic myeloproliferative disorders. The ability of interferon-alpha to induce hematologic and cytogenetic remission in chronic phase chronic granulocytic leukemia has further increased interest in this agent. Interferon-alpha has shown therapeutic activity in PV and ET, as demonstrated in multiple small studies and single-arm trials reviewed in this article. Reported beneficial effects include the ability to control excessive erythrocytosis and thrombocytosis and such disease-related features as vasomotor symptoms, pruritus, and splenomegaly. Recent reports of cytogenetic remission and reversal of bone marrow fibrosis after interferon therapy are of interest. Advantages over current therapeutic standards include lack of known leukemogenic and teratogenic effects and the potential to alter the underlying course of disease. Nevertheless, none of the information available allows definite therapeutic recommendations for the use of interferon-alpha in PV or ET. The available data support the need for randomized controlled trials comparing interferon-alpha with standard therapy.
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PMID:Interferon-alpha therapy in polycythemia vera and essential thrombocythemia. 938 5

Eighteen patients with polycythemia vera who were less than 60 years old received human leukocyte interferon-alpha subcutaneously at a starting dose of 3 MU three times a week. The interferon dose was escalated to 6 MU three times a week if it was well tolerated and disease was not controlled after 3 months of treatment at the lower dose. Hematologic response was defined as complete if the hematocrit was maintained at less than 45% in the absence of phlebotomy and partial if the hematocrit was kept at 45% to 50%, associated with a 50% or greater reduction of phlebotomy requirements; no response was defined as a response less than a partial response. Complete disease control was achieved in 11 patients, with partial control in a further six cases. One patient failed to respond. Median duration of response was 16 months (range 5 to 43 months), with 15 patients still under treatment. Therapy with human leukocyte interferon-alpha significantly improved (p <.01) phlebotomy requirements, the degree of splenomegaly, pruritus scores, iron stores and mean red cell volume values, and platelet and leukocyte counts. Interferon treatment did not produce remarkable side effects and no patient withdrew from the study because of intolerance. We conclude that subcutaneous human leukocyte interferon-alpha is an effective and well-tolerated therapy in the management of polycythemia vera-associated myeloproliferation and pruritus in patients less than 60 years old.
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PMID:Role of human leukocyte interferon-alpha in the treatment of patients with polycythemia vera. 953 37

We present an 86-years-old woman's case with paralysis in her left hand of abrupt apparition, accompanied by arterial hypertension and dizziness. The investigation revealed erythrocytosis, leukocytosis, thrombocytosis, with normal arterial O2 saturation (O2 SAT), increased of his red cell volume and blood viscosity. The polycythaemia vera (PV) was diagnose and the paralysis disappeared, when 24 hours before a phlebotomy was practiced, and the function was recovered by the hand. We analysed the presents diagnostics criteria of the disease defined by Polycythaemia Vera Study Group (PVSG). The different treatments for PV are discussed; in addition to venesection, conventional treatment include chemotherapy with hydroxyurea and pipobroman, as well as the erythropheresis, -interferon and aspirin. All of the treatments are associated with complications; thrombotic in the case of phlebotomy; malignancies and gastrointestinal bleeding in the case of myelosuppressive treatments and aspirin. We think the optimal treatment for PV is a judicious combination of the available alternatives, depending on the phase of the disease, and the age of the patient.
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PMID:[Primary polycythaemia vera in the elderly]. 958 Jan 77

The chronic myeloproliferative syndromes are bone marrow stem cell disorders. An increase of cell counts of one or rather all three blood cell types is characteristic for these disorders. The most important diseases in this group are: chronic myelogenous/granulocytic leukemia, polycythemia rubra vera, osteomyelosclerosis or agnogenic myeloid metaplasia and essential thrombocythemia. The cells are normally differentiating in these diseases, while the control of cell dividing is abnormal and therefore the cells are produced and accumulated in excess. Splenomegaly is a common and characteristic clinical finding. The fibrotic or sclerotic transformation of the bone marrow can take place in all forms of the syndrome. Extramedullary haematopoiesis can occur in all of the above diseases, but it is most common in myelofibrosis/agnogenic myeloid metaplasia. In the last phase of the disease a terminal blastic crisis may terminate the course of chronic myeloproliferative diseases. The myeloproliferative disorders can be transformed in each other--the most common transformation is that of the polycythemia rubra vera into myelofibrosis. The greatest progress in the therapy of chronic myeloproliferative diseases is achieved in chronic myelogenous leukemia: bone marrow transplantation and interferon treatment (the latter also in essential thrombocythemia and polycythemia rubra vera) are routine modalities worldwide. A new drug, anagrelide is effective in the treatment of myeloproliferative thrombocytosis and thrombocythemia.
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PMID:[Chronic myeloproliferative diseases]. 971 44

According to strict clinical, hematological and morphological criteria, the Philadelphia (Ph) chromosome negative chronic myeloproliferative disorders essential thrombocythemia (ET), polycythemia vera (PV), and agnogenic myeloid (megakaryocytic/granulocytic) metaplasia (AMM) or idiopathic myelofibrosis (IMF) are three distinct disease entities with regard to clinical manifestations, natural history and outcome in terms of life expectancy. As clonality studies have clearly demonstrated that fibroblast proliferation in AMM, as well as in many other conditions such as advanced stages of Ph(+)-essential thrombocythemia, Ph(+)-granulocytic leukemia, and Ph(-)-polycythemia vera, is polyclonal indicating that myelofibrosis is secondary to the megakaryocytic granulocytic metaplasia in these various conditions, AMM is illogically labeled as IMF. As abnormal megakaryocytic granulocytic metaplasia is the essential feature preceding the early prefibrotic stage of AMM, the term essential megakaryocytic granulocytic metaplasia (EMGM) can readily be used to characterize this condition more appropriately at the biological level. Clinical, hematological and morphological characteristics, in particular megakaryocytopoiesis and bone marrow cellularity, reveal diagnostic features, which enable a clear-cut distinction between ET, PV and EMGM or classical IMF. The characteristic increase and clustering of enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or only slightly increased cellular bone marrow represent the hallmark of ET. The characteristic increase and clustering of enlarged mature and pleiomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses are the specific diagnostic features of untreated PV. EMGM, including the early prefibrotic stages as well as the various myelofibrotic stages of classical IMF appear to be a distinct neoplastic dual proliferation of abnormal megakaryopoiesis and granulopoiesis. The histopathology of the bone marrow in prefibrotic EMGM and in classical IMF is dominated by atypical, enlarged and immature megakaryocytes with cloud-like immature nuclei, which are not seen in ET and PV at diagnosis and during follow-up. Myelofibrosis in ET, PV and EMGM is graded into: no reticulin fibrosis (MF0), early reticulin fibrosis (MF1), advanced reticulin sclerosis with minor or moderate collagen fibrosis (MF2) and advanced collagen fibrosis with osteosclerosis (MF3). Myelofibrosis is not a feature of ET at diagnosis and during long-term follow-up. Myelofibrosis may be present in a minority of PV-patients at diagnosis and usually becomes apparent during long-term follow-up in the majority of PV-patients. Myelofibrosis secondary to the abnormal megakaryocytic and granulocytic myeloproliferation constitutes a prominent feature in the majority of EMGM/IMF at time of diagnosis and usually progresses more or less rapidly during the natural history of the disease. Life expectancy is normal in ET, normal during the 1st ten years and compromised during the 2nd ten years follow-up in PV, but significantly shortened in the prefibrotic stage of EMGM as well as in the various myelosclerotic stages of classical IMF. First line treatment options in prospective randomized clinical trials of newly diagnosed MPD-patients are control of platelet function with low-dose aspirin versus reduction of platelet count with anagrelide, interferon or hydroxyurea in ET; control of platelet and erythrocyte counts by interferon alone versus bloodletting plus hydroxyurea on indication in PV; interferon versus no treatment in the early stages of EMGM; a wait and see strategy in the fibrotic stages of EMGM or classical IMF with favorable prognostic factors, and bone marrow transplantation in classical IMF with poor prognostic factors at presentation or during short-term follow-up.
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PMID:Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis. 1007 79

The importance of each of the two interferon (IFN) systems in impeding herpesvirus replication and in stimulating virus-specific lymphocytes to control an acute systemic infection is not completely understood. To further our knowledge, pseudorabies virus, attenuated by deletion of the glycoprotein E gene to impair its neurovirulence and by deletion of the thymidine kinase gene (gE-TK-PRV), was used to infect wild-type 129Sv/Ev and congenic mice with immune system-associated genetic deficiencies. Mice with mature B and T lymphocytes but lacking either one or both functional receptors for members of each of the two IFN families were infected with gE-TK-PRV. At 3 and 7 but not 14 days after infection, replicating gE-TK-PRV could be isolated only from livers or spleens of mice lacking the receptors for both IFN families, and these mice survived the infection. Therefore, functional IFN receptors were not required to induce a protective immune response against an acute infection with gE-TK-PRV. Furthermore, PRV-specific antibodies of all immunoglobulin G isotypes were produced in these mice. Mice without mature B and T lymphocytes and lacking either one or both functional receptors for members of each of the two IFN families were also infected with gE-TK-PRV. Three days after infection, replicating virus could be isolated only from mice lacking both mature B and T lymphocytes and functional IFN receptors, and these mice were not able to clear the virus. We present evidence that mice with an intact gamma IFN system but without mature B and T cells were able to prevent systemic dissemination of gE-TK-PRV.
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PMID:Role of the individual interferon systems and specific immunity in mice in controlling systemic dissemination of attenuated pseudorabies virus infection. 1023 35

Polycythaemia vera (PV) is a myeloproliferative disorder (MPD) characterized by an increased production of mature blood cells. The underlying pathogenic mechanisms behind PV are largely unknown. Thrombopoietin (TPO) is the most important cytokine for stimulation of megakaryocyte growth and formation of functional platelets. Recently, it has been shown that the receptor for TPO, c-mpl, is expressed on haematopoietic stem cells, and that TPO promotes the growth of these stem cells via binding to c-mpl. Quantitative or qualitative abnormalities of c-mpl function could thus theoretically play a role in the pathogenesis of different MPDs. Previous studies of the integrity of the c-mpl system in PV have produced conflicting results. We therefore studied c-mpl protein expression using immunoblot analysis in 15 PV patients and 10 healthy controls. Seven out of 15 PV patients (47%) exhibited similar c-mpl protein levels to the controls, whereas eight out of 15 patients (53%) showed either markedly reduced or absent levels of c-mpl. Five of the seven c-mpl-positive patients had only been treated by phlebotomy, whereas six out of eight c-mpl-negative patients were receiving treatment with hydroxyurea, anagrelide or alpha-interferon. Disease duration tended to be slightly longer in c-mpl-negative patients compared with c-mpl-positive patients (mean = 55 vs. 43 months). Tyrosine phosphorylation of JAK-2 in immunoprecipitates of platelets obtained after stimulation with TPO (100 and 1000 ng/ml) was normal in c-mpl-positive patients, whereas it could not be detected in c-mpl-negative patients. We therefore conclude that there exists a marked heterogeneity in c-mpl protein levels and functional integrity in PV. However, it seems less likely that c-mpl abnormalities per se are directly involved in the pathogenesis leading to the occurrence of PV, as c-mpl levels were similar to those seen in healthy individuals in about half of the patients under study.
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PMID:Marked heterogeneity in protein levels and functional integrity of the thrombopoietin receptor c-mpl in polycythaemia vera. 1065 27


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