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)

In a retrospective study over a period of 10 years we found 16 patients with Osler's disease and associated pulmonary arteriovenous fistulas in the hospital of the University of Heidelberg and the Thoraxklinik Heidelberg-Rohrbach. We report about the radiologic diagnostic findings and the clinical manifestations of this defined pulmonary malformation. Radiologic findings are round or oval lobulated homogeneous masses. The size ranges from < 1 to several centimeters in diameter, most fistulas were located in the lower lobes. Feeding and draining vessels can be identified frequently on plain radiographs or tomograms/CT. Best procedure to recognize these malformations is the selective pulmonary arterial angiography.
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PMID:[Pulmonary arteriovenous fistulas in Osler's disease]. 146 86

The chronic myeloproliferative disorders (MPD) comprise polycythemia vera (PV), idiopathic thrombocythemia (IT), chronic myeloid leukemia (CML) and myelofibrosis/osteomyelosclerosis (MF/OMS). Bone marrow biopsies of 3500 patients with known or suspected MPD were studied, and the clinical and morphologic variables registered were utilized for multivariate data analysis by selected BMD computer programs. The histologic criteria and the histologic subdivisions, as well as the evolution and prognosis of disease are outlined for each of the clinical entities. The results show that a bone marrow biopsy provides independent diagnostic and prognostic data in this group of hematologic malignancies and therefore constitutes an additional parameter in the diagnostic investigation of patients with suspected or established MPD.
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PMID:Potential of bone marrow biopsy in chronic myeloproliferative disorders (MPD). 843 14

The molecular basis of polycythemia vera is discussed in the context of the JAK2 V617F mutation, in our view the most important advance in understanding the pathogenesis of polycythemia vera. This chapter discusses the nature of the JAK2 V617F mutation including the studies demonstrating its role in erythropoietin independence and hypersensitivity and endogenous erythroid colony formation. The evolving evidence that JAK2 V617F is not specific for polycythemia vera pathogenesis and the development of disease phenotype is presented as well as alternative candidates for pathogenic mutations such as the protein tyrosine phosphatases and SOCS-3. Finally, the clinical correlations and implications of the JAK2 V617F mutation are discussed.
Best Pract Res Clin Haematol 2006
PMID:Polycythemia vera and its molecular basis: an update. 1678 79

Histopathology of bone marrow (BM) biopsies plays a crucial role in the interdisciplinary approach to diagnosis and classification of chronic myeloproliferative disorders (CMPDs). Based on careful clinicopathologic studies, BM features are critical determinants that help to predict overall prognosis, to detect complications such as progression to myelofibrosis and blast crisis, and to assess therapy-related changes. A systematic evaluation of BM histopathology allows an objective identification of cases of (true) essential thrombocythemia (ET) and their separation from (false) ET, which often is the prodromal stage of chronic idiopathic myelofibrosis (CIMF). By follow-up examinations that include BM biopsies, the progression of the disease process is unveiled, which is especially important for patients with initial (early) polycythemia vera and prefibrotic CIMF that may require a different therapeutic approach than the full-blown stages. In conclusion, BM biopsy should be considered as major diagnostic tool for evaluation and follow-up of patients enrolled in prospective studies.
Best Pract Res Clin Haematol 2006
PMID:Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: a forgotten pearl. 1678 81

Pathogenetically fundamental observations have identified polycythemia vera (PV) as a clonal stem cell disease with bone marrow histological and other biological features that distinctly differentiate it from other causes of 'increased' hematocrit. However, relatively little attention has been given to the effective utilization of pathology and laboratory markers of clonal myeloproliferation as diagnostic tools in PV. In contrast, the diagnostic use of red cell mass (RCM) measurement in PV stemmed from the accidental endorsement, as 'diagnostic criteria', of 'study eligibility criteria' that were formulated for clinical trials. It has since become evident that RCM measurement is a tedious procedure that is fraught with multiple-level imprecision, as well as suboptimal diagnostic accuracy. Therefore, it is reasonable to consider dispensing with RCM measurement as a diagnostic test for PV and instead utilize a diagnostic algorithm that combines clinical information with easily accessible laboratory data, including serum erythropoietin level and bone marrow histology. Recent discoveries of myeloproliferative-disease-specific molecular markers, including the JAK2 V617F tyrosine kinase mutation that is found in the majority of patients with PV, provide further support for such a measure.
Best Pract Res Clin Haematol 2006
PMID:The diagnosis of polycythemia vera: new tests and old dictums. 1678 83

Idiopathic erythrocytosis (IE) is characterized by an increase of red blood cell mass without an identified cause. Its diagnosis is based on the exclusion of polycythemia vera (PV), secondary acquired polycythemias and various congenital primary and secondary polycythemias. The frequency of IE has been estimated to be 1.1 per 1000 subjects, which is higher than that observed in PV. Heterogeneous mechanisms underlying IE have been suggested, including 'early' PV and unrecognized secondary or congenital polycythemia. However, the transition of a patient initially classified as IE into PV is a rare occurrence, when more sophisticated diagnostic techniques are employed. IE is a stable disease with a low thrombotic risk and a low, if any, tendency to spontaneous progression to acute leukemia or myelofibrosis. Phlebotomy in patients with IE is controversial. Myelosuppressive drugs should be avoided since their use is associated with evolution into acute leukemia in about 10% of patients.
Best Pract Res Clin Haematol 2006
PMID:Idiopathic erythrocytosis and other non-clonal polycythemias. 1678 84

The clinical course of polycythemia vera is marked by significant thrombotic complications and a variable risk of the disease turning either into myeloid metaplasia with myelofibrosis or into acute myeloid leukemia. Cytoreductive treatment of blood hyperviscosity by phlebotomy or chemotherapy and antiplatelet therapy with low-dose aspirin have dramatically reduced the number of thrombotic complications and substantially improved survival. However, there is concern that certain myelosuppressive drugs accelerate the disease progression to acute leukemia. Thus, the objective of management is two-fold: first, to minimize the risk of thrombotic complications; second, to prevent progression to myelofibrotic or leukemic transformation. This chapter provides updated estimates of the risk of thrombosis and disease progression and evaluates the various randomized and observational studies in polycythemia vera, according to an evidence-based approach.
Best Pract Res Clin Haematol 2006
PMID:Evidence-based management of polycythemia vera. 1678 85

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (i.e. not yet molecularly defined) myeloproliferative disorder (MPD), along with essential thrombocythemia (ET) and polycythemia vera (PV). All three MPDs represent stem-cell-derived clonal myeloproliferation that, in the case of MMM, is accompanied by an intense bone marrow stromal reaction that includes collagen fibrosis, osteosclerosis, and angiogenesis. To date, both the molecular basis of the primary clonal process and the pathogenetic mechanisms that underlie the secondary histological changes remain elusive. Clinically, MMM is characterized by anemia, multi-organ extramedullary hematopoiesis that often involves the spleen and liver, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Current diagnosis is based on characteristic but not diagnostic bone marrow histological features. Modern therapy remains palliative but allogeneic stem cell transplantation might be curative to a selected group of patients. This chapter reviews both the old and the new therapy with regard to non-transplant treatment options for MMM.
Best Pract Res Clin Haematol 2006
PMID:Myelofibrosis with myeloid metaplasia: disease overview and non-transplant treatment options. 1678 86

Polycythemia vera and essential thrombocythemia are chronic myeloproliferative disorders, the benign clinical course of which can be complicated by both thrombotic and hemorrhagic diatheses. Thrombotic diathesis is characterized by microcirculatory disturbances and by an increased risk of arterial and venous thromboses. Thrombotic accidents often manifest at diagnosis or in the preclinical phase of the disease so that the search for a latent myeloproliferative disorder has become widely recommended in screenings for acquired thrombophilia, particularly when venous thromboses manifest at an unusual site. Hemorrhagic diathesis is more rare, less ominous and mostly affects patients with a very high platelet count. In these subjects, an altered degradation and function of von Willebrand factor can cause minor mucocutaneous hemorrhages, which are sometimes a prelude to major gastrointestinal bleedings. The bleeding tendency can be effectively treated by cytoreduction. Pathogenesis and treatment of thrombotic diathesis are still controversial. The nature of disease-related hemostatic abnormalities and the role of common risk factors are far from being elucidated. In polycythemic subjects, treatment of blood hyperviscosity is essential and low-dose aspirin, which has an established antithrombotic efficacy, should always be used in the absence of contraindications. These are mostly constituted by conditions of increased bleeding risk, which, in particular, have to be evaluated when considering aspirin use in patients with essential thrombocythemia. Future clinical research should primarily aim to assess the risk/benefit ratio of aspirin use in this disease, to better characterize the determinants of vascular risk and to reduce the high incidence of leukemias in patients with these diseases. This might require either the availability of safer cytoreductive agents or, alternatively, the use of more aggressive antiplatelet regimens in patients at high thrombotic risk.
Best Pract Res Clin Haematol 2006
PMID:Thrombosis and bleeding in polycythemia vera and essential thrombocythemia: pathogenetic mechanisms and prevention. 1678 91

In 1951, William Dameshek speculated on the common origin of the chronic myeloproliferative disorders--polycythemia vera (PV), essential thrombocythemia (ET), chronic idiopathic myelofibrosis (IMF), and chronic myelogenous leukemia (CML). Subsequent work suggested that all arose from the hematopoietic stem cell. About 20 years ago the oncogene responsible for CML, bcr-abl, was identified, and more recently the mutant genes that cause hypereosinophilic syndrome and systemic mast cell disorder have been discovered. However, until very recently, the origin of PV, ET, and IMF have defied molecular explanation. In 2005, four separate groups working on tyrosine kinase signal transduction reported a gain-of-function, valine-to-phenyalanine, mutation at position 617 in the JH2 domain of the Janus kinase (JAK) 2 cytoplasmic tyrosine kinase. This mutation requires the presence of the erythropoietin, thrombopoietin, or granulocyte-colony stimulating factor receptor/s for function, the mutation leads to functional hyperactivity and appears responsible for hematopoietic growth factor hypersensitivity, the most characteristic finding in these disorders. Virtually all patients with PV and substantial proportions of those with ET and IMF have now been shown to harbor this mutation. The mutant kinase appears to be a useful diagnostic test for myeloproliferative disorders and may have prognostic value. Future research will undoubtedly focus on the development of specific inhibitors as therapeutic agents as well as answering a number of questions that remain regarding the role of signal intensity, genotypic and phenotypic expression and the possible involvement of additional as yet unidentified mutations in these disorders.
Best Pract Res Clin Haematol 2007 Mar
PMID:The chronic myeloproliferative disorders and mutation of JAK2: Dameshek's 54 year old speculation comes of age. 1733 49


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