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)

We report clinical and laboratory findings in a large cohort of patients with thrombocytosis (357 cases). At the time of study, the patients showed a platelet number greater than 500 x 10(9)/L. The follow-up of patients ranged between 3 and 16 years. 123 patients were affected by polycythemia vera (PV), 97 by essential thrombocythemia (ET), 13 by chronic myeloid leukemia (CML) and 31 by myelofibrosis (MF). In 93 subjects, the thrombocytosis was reactive (ST). We found the highest incidence of thrombosis in PV patients, especially concerning the cerebro-vascular system; thrombosis, but in a lower percentage, was recognized in MF patients. Also, ET patients showed a number of thrombosis in peripheral arteries. Thrombosis of the coronary arteries were quite rare while 25% of MPD subjects showed peripheral vein thrombosis. We take into account that many patients showed thrombocytosis associated to one or more atherosclerotic risk factors. Hemorrhages were present especially in CML and in ET, but were not as frequent as thrombosis. The most common bleeding manifestations affected skin and mucosa. Hemorrhages after surgical procedures were also frequent. Gastro-intestinal bleeding was not strictly related to anti-aggregating therapy and occurred not only in PV but also in ET patients.
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PMID:Thrombosis and hemorrhage in thrombocytosis: evaluation of a large cohort of patients (357 cases). 178 83

Restriction fragment length polymorphisms of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used to study clonality in peripheral blood leukocytes from 48 women with chronic myeloproliferative disorders (c-MPD). A total of 50% of patients were heterozygous for one or both of the polymorphic loci. These included 17 cases with polycythemia vera, four patients with essential thrombocythemia (ET), and three cases with idiopathic myelofibrosis (IMF). A clear-cut monoclonal X-inactivation pattern was observed in 17 of 24 cases including all IMF patients. Only one patient with PV exhibited a nonclonal composition of her leukocytes, while six cases demonstrated a predominantly clonal pattern in peripheral blood cells. Among the latter category reckoned three of four ET patients. Cell separation analyses were performed in one ET and three PV patients. In all four cases a monoclonal pattern of the granulocyte fraction could be established, while T lymphocytes of these patients were of nonclonal origin. These data suggest that the vast majority of c-MPDs arise from multipotent hematopoietic stem cells. Moreover, this type of clonal analysis might be of help in discriminating between primary MPD and reactive processes.
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PMID:Clonal analysis of chronic myeloproliferative disorders using X-linked DNA polymorphisms. 197 5

The incidence of monoclonal gammopathy in 61 patients with chronic myeloproliferative disorders (CMPD) was studied. The distribution of patients among the CMPD subgroups was: chronic myelocytic leukemia, 24 patients; myelofibrosis, 11; polycythemia vera, 15; essential thrombocythemia, 7; unclassified MPD, 4 patients. Monoclonal gammopathy was found in 5 patients (8.2%). Two of these patients (1 IgA/k and 1 IgM/k) had myelofibrosis and 3 (2 IgG/k and 1 IgG/lambda) polycythemia vera. The presence of monoclonal gammopathy indicates an involvement of the lymphoplasmatic system in CMPD.
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PMID:Monoclonal gammopathy in chronic myeloproliferative disorders. 291 5

The human erythropoietin receptor (EpoR) gene has been cloned and characterized. Very few EpoR genetic abnormalities have been reported so far. Polycythemia vera (PV) is characterized by low/normal serum erythropoietin (Epo) levels with proposed Epo hypersensitivity. Myelodysplastic syndromes (MDS) are characterized by refractory anemia with variable serum Epo levels. Several reports have suggested EpoR abnormalities in both types of stem cell disorders. We analyzed DNA obtained from peripheral blood mononuclear cells of seven healthy controls, 20 patients with myeloproliferative disorders (MPD, 11 patients with PV, five agnogenic myeloid metaplasia with myelofibrosis, four essential thrombocytosis) and eight patients with refractory anemia with ringed sideroblasts (RARS), an MDS variant. The DNA was digested with four restriction enzymes (BamHI, Bgl II, Sacl and HindIII), followed by Southern blot, using a 32P radiolabeled probe, containing 1.5 kb of the human EpoR cDNA. All 20 MPD patients and seven out of the eight MDS patients demonstrated a restriction pattern which was identical to the seven normal controls, as well as to the erythroid cell line K562, and also consistent with the expected restriction map, for all four enzymes tested. One RARS patient had a normal pattern with three enzymes but a different one with HindIII. The HindIII 12 kb large band was replaced by a faint 12 kb band and a new (about 9 kb) band appeared. The EpoR restriction map and the normal pattern obtained with the other three enzymes suggest that this patient has a 3 kb upstream deletion in one allelic EpoR gene. The same molecular pattern was detected in the patient's sister, who suffers from anemia with mild bone marrow (BM) dyserythropoiesis and plasmacytosis. Northern blot analysis showed that the patient's BM RNA carried normal EpoR message. This familial pattern may represent polymorphism. However, the patient's very high serum Epo level, her resistance to treatment with recombinant Epo, and the abnormally low growth rate of in vitro erythroid cultures, suggesting poor response to Epo in this MDS patient as well as the hematological abnormalities in her sister, support the speculation that the different EpoR gene might serve as a genetic predisposing marker and potentially could be involved (probably via post-transcriptional mechanisms and by an interaction with other factors or cytokines) in the pathogenesis. Our data suggest that the EpoR is intact in MPD and in most patients with RARS. One RARS patient had a familial different genetic structure, which could represent polymorphism. However, we can speculate also that it might be involved in the pathogenesis of the disease.
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PMID:Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes. 870 17

The telomerase activity of various hematologic disorders, including malignant and non-malignant ones is discussed in this paper. In total of 137 cases, each positivity of telomerase activity was MDS = 17/51, overt leukemia from MDS = 6/15, AML = 17/21, ALL = 4/6, CML-CP (chronic phase) = 0/10, CML-BC (blastic crisis) = 4/4, MPD (myeloproliferative disease)-BC = 3/3, CLL = 1/10, MM (multiple myeloma) = 0/6, aplastic anemia = 3/5, essential thrombocytosis = 0/3, and polycythemia vera = 1/3. The MPD-BC showed very high level of telomerase activity as well as CML-BC cases. From the analysis for 18 cases of AML and/or malignant lymphoma patients, significant results showed that the expression of cyclin D/E was not related to telomerase activity in these hematologic disease, as was not the case with breast cancer which was reported formerly.
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PMID:[Analysis for telomerase activity in various hematologic disorders]. 961 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

Clinical, hematological and morphological peripheral blood and bone marrow characteristics, in particular, megakaryopoiesis and bone marrow cellularity, reveal diagnostic clues and pathognomonic features, which enable a clear-cut distinction between essential thrombocythemia (ET), polycythemia vera (PV) and prefibrotic and fibrotic agnogenic myeloid metaplasia (AMM). The characteristic increase of enlarged mature megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or 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. ET may precede PV for many years to more than one decade. Prefibrotic and fibrotic AMM appears to be a distinct dual proliferation of abnormal megakaryopoiesis and myelopoiesis. The histopathology of the bone marrow in prefibrotic and fibrotic AMM 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 is not a feature of ET at diagnosis and during long-term follow-up. Myelofibrosis, which is secondary to the megakaryocytic/granulocytic myeloproliferation, and extramedullary myeloid metaplasia constitute a prominent feature and usually progress more or less rapidly during the natural history of PV and AMM. Life expectancy is normal in ET, normal in the first and decreased in the second decade of follow-up in PV, but significantly shortened in thrombocythemia associated with prefibrotic AMM as well as in the various fibrotic stages of AMM. These clinical and pathological characteristics of the Ph-negative MPDs, by including bone marrow histopathology, enable a clear-cut distinction between ET, PV and prefibrotic and fibrotic AMM. The use of established and new biological markers of MPDs, like spontaneous EEC, PRV-1 gene expression etc, should be validated in large prospective multicenter studies of newly diagnosed and previously treated MPD patients using the proposed European clinical and pathological (ECP) criteria as the only gold standard available for the proper diagnosis and differential diagnosis of ET, PV and AMM.
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PMID:Bone marrow histopathology and biological markers as specific clues to the differential diagnosis of essential thrombocythemia, polycythemia vera and prefibrotic or fibrotic agnogenic myeloid metaplasia. 1504 58

The combined use of bone marrow histopathology, biomarkers and clinical features has the potential to diagnose, stage and distinguish early and overt stages of ET, PV and idiopathic myelofibrosis, that has an important impact on prognosis and treatment of MPD patients. As the extension of the PVSG and WHO for ET, PV and agnogenic myeloid metaplasia (AMM), a new set of European clinical and pathological (ECP) criteria clearly distinct true ET from early or latent PV mimicking true ET, overt and advanced polycythemia vera (PV), and from thrombocythemia associated with prefibotic, early fibrotic stages of chronic megakaryocytic granulocytic metaplasia (CMGM) or chronic idiopathic myelofibrosis (CIMF). Cases of atypical MPD and masked PV are usually overlooked by clinicians and pathologists. Bone marrow biopsy will not differentiate between post-PV myelofibrosis versus so-called classical agnogenic myeloid metaplasia. The recent discovery of the JAK2 V617F mutation can readily explain the trilinear megakaryocytic, erythroid and granulocytic proliferation in the bone marrow, but also the etiology of the platelet-mediated microvascular thrombotic complications at increased platelet counts and red cell mass in essential thrombocythemia and polycythemia vera.
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PMID:Clinical, pathological and molecular features of the chronic myeloproliferative disorders: MPD 2005 and beyond. 1618 76

The rationale of the Czech Hematological Society guidelines for diagnosis and treatment of Philadelphia chromosome-negative myeloproliferative disorders with thrombocythemia (MPD-T) is reviewed. For diagnosis of MPD-T, the classification according to the World Health Organization or to the Rotterdam criteria is preferred because they distinguish true essential thrombocythemia from prefibrotic or early fibrotic idiopathic myelofibrosis and prepolycythemic polycythemia vera. The histopathology-based nosological distinction provided by these classifications yields valuable information on prognosis (including the risks of transition into secondary acute myeloid leukemia and myelofibrosis). Another serious complication in MPD-T is thrombosis (arterial or venous), the main risk factors of which are age, previous thrombosis, platelet counts 350 to 2,200 x 10 (9)/L (peak at approximately 900 x 10 (9)/L) and the presence of additional thrombophilic risk factors (hereditary thrombophilia, any hypercoagulable state, cardiovascular disease). The hemorrhagic risk starts increasing progressively at platelet counts > 1,000 x 10 (9)/L. Treatment should be stratified with respect to the thrombotic and hemorrhagic risks. In high-risk patients, thromboreductive therapy is warranted. All of the cytostatic drugs, including hydroxyurea, may be leukemogenic and should be given only to patients > 60 years old, whereas anagrelide or interferon alpha are preferred in younger individuals. In low-risk patients, antiaggregation therapy is sufficient, unless the platelet count exceeds 1,000 x 10 (9)/L, which is another indication for thromboreduction. Thrombopheresis is indicated in thrombocythemia > 2,000 x 10 (9)/L.
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PMID:Analysis of risk factors: the rationale of the guidelines of the Czech Hematological Society for diagnosis and treatment of chronic myeloproliferative disorders with thrombocythemia. 1667 77

Hydroxyurea (HU) is effective in controlling thrombocytosis while reducing the risk of thrombosis in essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). However, HU may carry more or less severe side-effects. Rare cases of patients with painful leg ulcers have been published. We report our experience on such a side-effect in a large cohort of patients with ET and PV treated with HU and review the literature on the topic. Five (4%) out of our 124 patients (69 ET, 51 PV, 4 MF; 49 males, 75 females; mean age at diagnosis 59.1+/-11.8 years) treated with HU developed painful leg ulcers. Sixty-one other patients affected with Phmyeloproliferative disorders (Ph- MPD) developing HU-related painful leg ulcers are described in the English literature. All our five patients were women and developed leg ulcers over the age of 75. Sixty-five percent of all described cases are women; 59% were over 65 years of age and 45% over 70. Most cases received over 1 gr HU per day for at least 1 year. The pathogenesis of HU-induced skin ulcers remains elusive. Treatment is difficult and requires prompt cessation of HU therapy.
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PMID:Leg ulcers in elderly on hydroxyurea: a single center experience in Ph- myeloproliferative disorders and review of literature. 1680 63


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