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)

The diagnosis of essential thrombocythemia in a cat was made by fulfilling the five applicable criteria set forth by the Polycythemia Vera Study Group for use in humans. The criteria were 1) a platelet count persistently above 600,000/microL, 2) a normal initial hematocrit that did not rise in response to iron therapy, 3) normal serum iron concentration, 4) absence of collagen fibrosis of the bone marrow, and 5) no cause for reactive thrombocytosis. In addition, normal thrombopoietin concentrations and splenic hypofunction were demonstrated. Melphalan was not effective in decreasing the platelet count and the cat died of sepsis.
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PMID:Essential thrombocythemia in a cat. 234 25

Megakaryocyte proliferation in bone marrow is a feature common to the three Philadelphia negative chromosome myeloproliferative disorders (MPD)--essential thrombocythemia (ET), polycythemia vera, and myelofibrosis with splenic myeloid metaplasia--and chronic myelocytic leukemia. Enlarged megakaryocytes, clustering in close neighbouring with multilobulated nuclei are the hallmark of all the Philadelphia negative chromosome MPD. Clonality of hematopoietic cells, based on X-chromosome inactivation can now be studied in a majority of female patients in all nucleated cell fractions as well as in platelets. A significant increase in circulating CFU-MK has been repeatedly observed in MPD as well as a spontaneous megakaryocyte colony formation in a majority of ET patients. Hypersensitivity to thrombopoietin (TPO) in relation with a functional defect of the TPO-MPL pathway may play a major role in spontaneous megakaryocyte growth. There is presently no currently available test of platelet functions able to predict the risk of occurrence of thrombotic or haemorrhagic complications in MPD patients. However the role of platelets activation in the pathogenesis of ischemic erythromelalgia has been established.
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PMID:[Dysmegakaryocytopoiesis and dysthrombopoiesis in myeloproliferative syndromes]. 907 18

Although all blood cells are derived from hematopoietic stem cells, the regulation of this production system is only partially understood. Negative feedback control mediated by erythropoietin and thrombopoietin regulates erythrocyte and platelet production, respectively, but the regulation of leukocyte levels is less well understood. The local regulatory mechanisms within the hematopoietic stem cells are also not well characterized at this point. Because of their dynamic character, cyclical neutropenia and other periodic hematological disorders offer a rare opportunity to more fully understand the nature of these regulatory processes. We review the salient clinical and laboratory features of cyclical neutropenia (and the less common disorders periodic chronic myelogenous leukemia, periodic auto-immune hemolytic anemia, polycythemia vera, aplastic anemia, and cyclical thrombocytopenia) and the insight into these diseases afforded by mathematical modeling. We argue that the available evidence indicates that the locus of the defect in most of these dynamic diseases is at the stem cell level (auto-immune hemolytic anemia and cyclical thrombocytopenia seem to be the exceptions). Abnormal responses to growth factors or accelerated cell loss through apoptosis may play an important role in the genesis of these disorders.
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PMID:Cyclical neutropenia and other periodic hematological disorders: a review of mechanisms and mathematical models. 1038 93

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

Essential thrombocythaemia (ET) is usually considered a disease of the middle-aged but, with the advent of automated platelet counting, ET is diagnosed with increasing frequency in young adults and, even more rarely, in children. We report five paediatric patients (four girls and one boy, mean age 89 months) diagnosed with ET in agreement with Polycythaemia Vera Study Group criteria. The patients had a persistent thrombocytosis over 900 x 10(9)/l and, at the time of diagnosis, their platelet count ranged between 1,112 and 3,178 x 10(9)/l. A 9-month-old girl had thrombosis of the inferior cava vein, two children had headaches and two others remained asymptomatic throughout the follow-up period. Megakaryocytes in the bone marrow were increased in number. The chromosomal analysis was normal, and bcr rearrangement was always negative. None of the patients had spontaneous BFU-E or altered levels of serum erythropoietin and thrombopoietin. Two patients showed alteration of platelet aggregation, and all had decreased levels of intraplatelet serotonin. In spite of the diagnosis of ET in our patients, we are not sure that the cases reported here are really myeloproliferative disorders. The features could suggest that the cases observed may be affected by an 'idiopathic thrombocytosis' without myeloproliferation. Possible variants of ET are described in young adults, and the heterogeneous nature of ET is also suggested by our paediatric patients. Only careful long-term follow-up of patients such as these will clarify the natural history of these disorders and suggest therapeutic management.
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PMID:Features of essential thrombocythaemia in childhood: a study of five children. 1120 8

We describe a boy with XYY male accompanied with essential thrombocythemia. This is, to our knowledge, the first complete case report of the kind in the pediatric literature. The patient was asymptomatic, but at age 5 his platelet count had increased to 145.5 x 10(4)/microL, and he was diagnosed as having essential thrombocythemia based on the diagnostic criteria of the Polycythemia Vera Study Group. At that time, it was discovered by chromosome analysis of both bone marrow and peripheral blood cells that he was XYY male. At times during the clinical course when his platelet count was 94.1 x 10(4)/microL, his serum thrombopoietin (measured by enzyme-linked immunosorbent assay) was 1.09 fmol/mL, which was normal for his age. Aspirin was administered, and he remained asymptomatic throughout the course. After 2 years, he underwent a spontaneous remission. Because of the small number of reported cases, we have been unable to determine the relation between XYY males and essential thrombocythemia.
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PMID:XYY male with essential thrombocythemia in childhood. 1072 94

Two prospectively studied patients with polycythemia vera (PV) whose platelet counts showed marked periodic fluctuation during treatment with hydroxyurea (HU) are reported. Cycle lengths in both were approximately 28 to 30 days. In one patient, the cyclic process was no longer evident when treatment with HU was withheld, and it reappeared on treatment rechallenge. Circulating thrombopoietin (TPO) levels fluctuated out of phase with the platelet count despite markedly reduced TPO-receptor (c-Mpl) expression in bone marrow megakaryocytes. These observations suggest that the cyclic phenomenon may be related to both a transient state of HU-induced depletion of megakaryocytes and a concentration-dependent mitigation by TPO of the HU effect on megakaryocytes and their precursors. It is conceivable that the affected patients harbor a megakaryocyte progenitor pool whose apoptotic activity is differently modulated by either HU or high concentrations of TPO. (Blood. 2000;96:1582-1584)
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PMID:Hydroxyurea-induced marked oscillations of platelet counts in patients with polycythemia vera. 1094 9

The pathogenesis of polycythemia vera (PV), a disease involving a multipotent hematopoietic progenitor cell, is unknown. Thrombopoietin (TPO) is a newly characterized hematopoietic growth factor which regulates the production of multipotent hematopoietic progenitor cells as well as platelets. To evaluate the possibility that an abnormality in TPO-mediated signal transduction might be involved in the pathogenesis of PV, we examined TPO-induced protein tyrosine phosphorylation using platelets as a surrogate model system. Platelets were isolated from the blood of patients with PV as well as from patients with other chronic myeloproliferative disorders and control subjects. Impaired TPO-mediated platelet protein tyrosine phosphorylation was a consistent observation in patients with PV as well as those with idiopathic myelofibrosis (IMF), in contrast to patients with essential thrombocytosis, chronic myelogenous leukemia, secondary erythrocytosis, iron deficiency anemia, hemochromatosis, or normal volunteers. Thrombin-mediated platelet protein tyrosine phosphorylation was intact in PV platelets as was expression of the appropriate tyrosine kinases and their cognate substrates. However, expression of the platelet TPO receptor, Mpl, as determined by immunoblotting, chemical crosslinking or flow cytometry was markedly reduced or absent in 34 of 34 PV patients and also in 13 of 14 IMF patients. Impaired TPO-induced protein tyrosine phosphorylation in PV and IMF platelets was uniformly associated with markedly reduced or absent expression of Mpl. We conclude that reduced expression of Mpl is a phenotypic characteristic of platelets from patients with PV and IMF. The abnormality appears to distinguish PV from other forms of erythrocytosis and may be involved in the platelet function defect associated with PV.
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PMID:A novel thrombopoietin signaling defect in polycythemia vera platelets. 1101 90

Hematopoietic progenitor cells in 2 myeloproliferative disorders, juvenile chronic myelomonocytic leukemia and polycythemia vera, are known to be hypersensitive to cytokines that control normal progenitor cell proliferation, differentiation, and survival in their respective granulocyte/macrophage and erythroid lineages. Because thrombopoietin controls these functions in the normal megakaryocytic lineage, we asked the question: Are megakaryocytic progenitor cells in the myeloproliferative disorder essential thrombocythemia (ET) hypersensitive to thrombopoietin? Peripheral blood mononuclear cells from patients with ET, or secondary (reactive) thrombocytosis (2 degrees T), or healthy volunteers were grown in strictly serum-free agarose culture containing interleukin 3 (IL-3) and all-trans-retinoic acid, with various concentrations of PEG-rHu megakaryocyte growth and development factor (MGDF). The concentration of cytokine at half-maximum colony number served as a measure of progenitor cell sensitivity. Hypersensitivity to PEG-rHu MGDF was found in circulating progenitors from 18 of 20 (90%) informative patients with presumptive diagnosis ET, 1 of 8 (12.5%) 2 degrees T patients, and none of the 22 healthy volunteers. Median MGDF sensitivity ratio in ET patients was approximately 53 times greater than in the controls. This hypersensitivity, which was also directed to rHu thrombopoietin, was highly specific with respect to cytokine, disease, and cell lineage. We propose that, despite their single pluripotential cell origin, the different clinicopathologic phenotypes in different chronic myeloproliferative disorders are determined by lineage-restricted hypersensitivities of hematopoietic progenitor cells to endogenous cytokines. This work emphasizes the importance of stringent serum-free conditions for revealing true sensitivities to cytokines. The findings also offer a basis for evolving a positive test for ET, a diagnosis now made essentially by exclusion.
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PMID:Hypersensitivity of circulating progenitor cells to megakaryocyte growth and development factor (PEG-rHu MGDF) in essential thrombocythemia. 1107 22

Essential thrombocythemia (ET) is one of the quite rare myeloproliferative disorders in children. The natural course and outcome of this disease have been reported to vary. We report three children (two boys and one girl, mean age at diagnosis 12 yr) with ET who showed different clinical courses. The girl was asymptomatic, but the boys had ankle pain and priapism, respectively. The platelet count ranged between 2300 and 2900 x 10(9)/L, and the diagnoses were made according to the criteria of the Polycythemia Vera Study Group. The serum thrombopoietin level reached 0.33 and 0.47 fmol/ml in two patients. All three children were administered aspirin or dipyridamole orally. Normalization of the platelet count was observed in two patients, and stable disease persisted in one. The 12 pediatric patients with ET reported previously in Japan demonstrated a low incidence of serious thrombohemorrhagic complications and a favorable outcome, none developing acute leukemia. Careful continuous observation and conservative treatment may be preferable in pediatric patients who do not have cardiovascular symptoms, avoiding the use of potential leukemogens such as alkylating agents and hydroxyurea.
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PMID:[Clinical features of essential thrombocythemia in three children]. 1119 34


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