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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients with choreatic syndromes caused by polycythemia vera recovered after treatment of the polycythemia by only two venesections: this proves that the syndrome is due to reversible alterations. Investigations of the cerebral circulation in one of the patients showed that blood flow was lowest in the grey matter at the basal region of the brain: this suggests that the alterations might mainly occur there. However, investigation of erythrocyte rheology, glucose-6-phosphate dehydrogenase, serum concentrations of caeruloplasmin and serotonin, and urinary excretion of epinephrine, norepinephrine and vanillylmandelic acid gave normal results in both patients. There are therefore no indications as to the possible pathophysiology of these alterations. There are now 24 cases reported, including our 2 patients, which suggests that the association of these two diseases may not be so rare as supposed.
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PMID:Two cases of choreatic syndrome caused by polycythemia vera. 45 93

In previous studies of two patients with polycythemia vera (PV) and heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G-6-PD), only type A isoenzyme was found in non-lymphoid hematopoietic cells. However, some granulocytic and erythrocytic colonies grown in vitro had type B G-6-PD and therefore arose from presumably normal progenitors. In this study we exposed marrow cells from these same two patients to high-specific activity tritiated thymidine (3HTdR) before culture to kill cells actively synthesizing DNA. Individual granulocytic colonies were plucked and tested for G-6-PD after 14 d of culture. The frequency of type B colonies rose after exposure to 3HTdR from 8/101 to 11/36 in patient 1 and from 0/32 to 6/31 in patient 2 (P less than 0.003). No increase in the frequency of normal erythroid bursts after 3HTdR exposure was seen, implying that in PV, early granulopoiesis, and erythropoiesis are regulated differently. The results demonstrated that only type A granulocytic colonies, arising from the abnormal clone, were removed by the 3HTdR. In addition, for patient 2, statistical analysis indicated there was an absolute increase in normal granulocytic colonies detected in culture. Thus, PV clonal colony-forming units in culture (CFU-C) cycle more rapidly than do normal CFU-C and may suppress proliferation of normal CFU-C in vitro.
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PMID:Polycythemia vera. Increased expression of normal committed granulocytic stem cells in vitro after exposure of marrow to tritiated thymidine. 50 Aug 13

Bone marrow cells from two glucose-6-phosphate dehydrogenase (G-6-PD) heterozygotes with polycythemia vera were cultured to determine whether progenitors which wre not of the polycythemia vera clone were present, and, if present, which cell lines contributed to the increase in erythroid colonies observed in response to added erythropoietin (ESF). To accomplish this, the G-6-PD isoenzyme activity of individual erythroid colonies was determined. All of the erythroid colonies analyzed in cultures without added ESF, contained the G-6-PD isoenzyme type characteristic of the abnormal clone. With higher ESF concentrations in the culture, however, there was an increase in the colonies that were not of the polycythemia vera clone. Analysis of the ratio of the various types of colonies indicated that normal and polycythemia vera cells are capable of responding to ESF in vitro. In selected patients, this technique permits analysis of the ratios of normal to abnormal cells during the course of the disease, in response to therapy and during late complications, such as myelofibrosis or leukemic transformation.
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PMID:Polycythemia vera. The in vitro response of normal and abnormal stem cell lines to erythropoietin. 65 76

Two women with polycythemia vera and heterozygosity (GdB/GdA) at the X-chromosome-linked locus for glucose-6-phosphate dehydrogenase were studied to determine the nature of the cellular origin of their polycythemia. In contrast to unaffected tissue, such as skin fibroblasts, which consisted of both B and A types, the glucose-6-phosphate dehydrogenase of the patients' erythrocytes, granulocytes and platelets was only of Type A. These results provide direct evidence for the stem-cell nature of polycythemia vera and strongly imply a clonal origin for this disease. The fact that no descendants of the presumed normal stem cells were found in circulation suggests that bone-marrow proliferation in this disorder is influenced by local (intramarrow) regulatory factors.
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PMID:Polycythemia vera: stem-cell and probable clonal origin of the disease. 96 1

Enzyme abnormalities are frequently found in the red cells of patients with various acquired blood disorders. In leukaemias, preleukaemic states and bone marrow insufficiencies with or without sideroblastosis, changes in enzyme activity are usually characterized by the coexistence of deficiency of some enzymes and an increased activity of others. The most frequently decreased activities are those of pyruvate kinase, phosphofructokinase,2,3-diphosphoglycerate mutase and adenylate kinase; the most frequently increased activities are those of hexokinase, aldolase, enolase, 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase. In primary myelofibrosis and in polycythaemia rubra vera, enzyme deficiencies are infrequent and differ from those observed in leukaemias and related disorders. Phosphohexose isomerase and phosphoglucomutase deficiencies seem relatively specific for polycythaemia rubra vera. Explanations for the acquired enzymopathies are still at the stage of hypothesis. The theory of multiple genetic damage may explain some findings but has not yet been proved right. The possibility of post-translational molecular modification is suggested as a working hypothesis.
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PMID:Acquired erythroenzymopathies in blood disorders: study of 200 cases. 107 44

Previous studies with the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD) as a marker of cellular mosaicism demonstrated that polycythemia vera (PV) and essential thrombocythemia (ET) are clonal disorders of hematopoietic stem cells that can differentiate to erythrocytes, granulocytes, and platelets. To determine if the involved stem cells could also differentiate along the B-lymphoid pathway, we studied one woman with PV and one woman with ET. Of 117 Epstein-Barr virus-transformed B-lymphoblastoid lines expressing a single G6PD derived from the patient with PV, 108 expressed G6PD type A, the type characteristic of the abnormal clone. The ratio of 108:9 was significantly different from the one to one ratio predicted for this patient, which suggested that at least some circulating progenitors for B-lymphoid cell lines differentiate from the stem cell involved by the disease. Results obtained from the patient with ET were similar--104 of the 109 lymphoblastoid lines monotypic for G6PD expression displayed the enzyme type found in the abnormal clone of marrow cells. Therefore, in these patients, PV and ET, like chronic myelogenous leukemia, involve a stem cell pluripotent for the lymphoid as well as the myeloid series.
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PMID:Evidence for the involvement of B lymphoid cells in polycythemia vera and essential thrombocythemia. 392 71

In previous studies of two patients with polycythemia vera (PV) who were heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G6PD), only A type enzyme was found in nonlymphoid blood cells. However, some erythroid and granulocytic colonies grown in vitro were type B and therefore arose from presumably normal progenitors. One patient had enough type B colonies (8%) that studies of the physical characteristics of normal and PV clonal colony-forming cells could be undertaken. When marrow cells were separated by velocity sedimentation at unit gravity, most PV clonal granulocyte-macrophage progenitors (CFU-C) (type A G6PD) sedimented between 6.4 and 7.2 mm/h, whereas most residual normal, type B CFU-C sedimented less than or equal to 5.9 mm/h (P = 0.04)., When blood cells were separated over a discontinuous buoyant density gradient, PV clonal CFU-C equilibrated at densities < 1.065 g/ml, whereas residual normal CFU-C were found greater than or equal to 1.065 g/ml (P < 0.01). PV clonal and residual normal erythroid burst-forming progenitors were not separable by either method. Thus PV clonal CFU-C are larger and less dense cells than are residual normal CFU-C.
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PMID:Polycythemia vera. Physical separation of normal and neoplastic committed granulocyte-macrophage progenitors. 693 5

Long-term cultures of marrow cells from ten normal subjects and three patients with polycythemia vera were established to compare normal and neoplastic hemopoiesis in vitro. Suspended cells were removed periodically from the cultures and assayed from their content of various colony-forming cells, including erythroid colony- and burst-forming cells (CFU-E and BFU-E), granulocyte/macrophage colony-forming (CFU-C), and "mixed cell" colony progenitors (CFU-GEMM). To determine if mixed cell colonies arise from a single progenitor, we used the cellular mosaicism conferred by X-chromosome inactivation. The isoenzymes of glucose-6-phosphate dehydrogenase (G-6-PD) were used as markers of the mosaicism. Preliminary results suggest that these colonies are clonal only at low plating densities. The G-6-PD system was also used to determine whether selection or "drift" occurs in continuous long-term cultures. The ratios of G-6-PD isoenzyme types in pooled colonies from cultures of two normal heterozygotes remained similar, indicating stable cultures. Long-term cultures of normal marrow and marrow from the patients with polycythemia vera maintained BFU-E for a mean of 8.7 (+/- 0.6) and 12.5 (+/- 0.5) weeks (P = 0.03), respectively. The fractions of total BFU-E detected as endogenous erythroid colonies remained similar over the culture period. These results demonstrate that 1) hemopoiesis in polycythemia vera can be analyzed in long-term culture; 2) polycythemia vera marrow grows as well or better than normal in long-term culture; and 3) the proportion of the neoplastic clone in polycythemia vera represented by endogenous erythroid colony growth is unchanged over time, suggesting no reemergence of normal stem cell progeny in this system.
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PMID:Polycythemia vera: studies of hemopoiesis in continuous long-term culture of human marrow. 695 Sep 47

Essential thrombocythemia is characterized by proliferation of hematopoietic tissue predominantly involving megakaryocytes and resulting in marked thrombocytosis. The disorder has some clinical and laboratory features that resemble those seen in the clonal multipotent stem cell disorders chronic myelogenous leukemia, polycythemia vera, and agnogenic myeloid metaplasia. It has been argued that essential thrombocythemia should be classified together with those disorders as a myeloproliferative syndrome. However, without knowledge of the numbers and types of cells that are involved in essential thrombocythemia, this suggestion remains speculative. Three patients with thrombocytosis were studied. The diagnosis of essential thrombocythemia was considered to be firm in two patients and probable in the third one. The X-linked glucose-6-phosphate dehydrogenase locus was used as a cell marker. Whereas both A and B types of glucose-6-phosphate dehydrogenase were found in nonhematopoietic tissues, only a single-enzyme type was found in the granulocytes, red cells, and platelets from each patient. These data indicate that the disorders in these three patients are clonal and involve multipotent stem cells.
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PMID:Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell. 729 2

The clonal origin of malignancy and hematopoiesis is a principal tenet of modern biology and medicine. This paper describes a highly specific and sensitive assay for the detection of clonality in cells and cell lineages suitable for studies in a large proportion of females. The specific ligase chain and/or ligase detection reactions (LCR/LDR) are utilized at a polymorphic glucose-6-phosphate dehydrogenase (G-6-PD) locus for discrimination of the mRNA transcripts of the active X chromosome. This combination approach circumvents problems encountered with other currently used assays of clonality based either on peptide G-6-PD polymorphism or on DNA methylation differences between the active and inactive X chromosomes. The veracity of this assay was verified by analysis of 19 random healthy females as well as by the study of hemopoietic and nonhemopoietic tissues from a patient with clonal hemopoiesis/polycythemia vera. Furthermore, we demonstrate that the G-6-PD locus used in our clonal assay does not display marked differences in methylation between the active and the inactive X chromosomes.
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PMID:A novel clonality assay based on transcriptional analysis of the active X chromosome. 831 21


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