Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycythemia vera (PV) is one of the myeloproliferative diseases, and, as such, is an example of clonal hematopoiesis. The progeny of a single, abnormal, hematopoietic stem cell gain a growth advantage over their normal counterparts resulting in overproduction of red cells generally accompanied by overproduction of granulocytes and platelets as well. There are a variety of nonspecific symptoms at onset related to the increased red cell mass and hematocrit accompanied by the more specific manifestations of pruritus, erythromelalgia, and hepatic, portal, and mesenteric vein thrombosis. Splenomegaly and hypertension are common. The laboratory hallmark is an increased red cell mass. There is also often an increase in white cell count, platelet count, and leukocyte alkaline phosphatase along with other findings reflecting the increased rate of turnover of hematopoietic cells. The bone marrow biopsy generally displays hypercellularity involving all three cell lines and absent iron stores. The diagnosis of PV depends on excluding spurious polycythemia in which there is a high hematocrit but a normal red cell mass and secondary polycythemia in which there is an increased red cell mass in response to tissue hypoxia or the inappropriate production of erythropoietin, generally by a tumor. In addition, one should try to establish the diagnosis in a positive fashion by a combination of studies of the blood and bone marrow. Phlebotomy and occasionally plateletpheresis should be used as acute therapy. Chronic therapy is guided by the knowledge that patients treated with phlebotomy alone have an increased rate of thrombotic complications particularly in older patients and those with previous thrombotic disease. Myelosuppressive therapy can reduce the incidence of these complications, but is commonly associated with an increased incidence of second malignancies, particularly acute leukemia. At present, hydroxyurea is the myelosuppressive agent of choice. Antiplatelet agents have a limited role except in the palliation of the syndrome of erythromelalgia. Median survival is approximately 10 years. As implied above, the causes of morbidity and mortality vary with the mode of chronic therapy which has been employed, leukemia being more common after myelosuppressive therapy and thrombotic complications being more common after therapy with phlebotomy alone. Ten percent to 50% of patients move into a spent phase followed by postpolycythemic myeloid metaplasia, irrespective of previous therapy employed. Eventually, the major problems may be cytopenias and massive splenomegaly.
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PMID:Polycythemia vera. 158 7

The monoclonal antibody Ki-S1 reacts with a cell proliferation-associated nuclear antigen which is expressed in the G1 through G2/M phases of the cell cycle and is resistant to formalin fixation. We have studied Ki-S1 and PCNA (PC10) immunostaining of erythroid precursors (proliferative activity) and megakaryocytes (endoreduplicative activity) in bone marrow trephine biopsies in a variety of reactive and neoplastic lesions using double immunohistochemistry to identify both cell lineages. A significant increase in Ki-S1 labelling compared with PCNA positivity was found in all conditions studied. In particular, specimens derived from secondary polycythaemia (SP), polycythaemia vera (P. vera), and primary osteomyelofibrosis (OMF), and from splenic tissue with myeloid metaplasia (MM), revealed a disproportionally high labelling index of erythropoiesis, which was not present in chronic myelogenous leukaemia (CML), AIDS, and autoimmune (idiopathic) thrombocytopenia (ITP). Enhancement of Ki-S1 (PCNA) staining in SP and P. vera is in keeping with the relevant increase in erythroid precursor proliferation, but in OMF and MM there is overexpression of both proliferation markers, possibly due to secondary folic acid deficiency, which is known to cause a block in the S-phase of the cell cycle. A significant correlation was observed between the sizes of megakaryocytes and their nuclei with Ki-S1 (and also PCNA) staining. Ki-S1 (and PCNA) labelling of predominantly smaller elements of this lineage supports a hypothesis that the phases of the cell cycle have different durations in the various steps of polyploidization, with a prolongation of G1/G2 at higher ploidy levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ki-S1 and PCNA expression in erythroid precursors and megakaryocytes--a comparative study on proliferative and endoreduplicative activity in reactive and neoplastic bone marrow lesions. 752 42

With a newly developed enzyme linked immunosorbent assay kit TOYOBO Co. in which 2 anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from normal adults, 168 patients with renal failure and 333 patients with hematological disorders. In the patients with renal failure, serum EPO level was normal (52.9%) or reduced (42.9%), and there was no correlation to their hematocrits. However, there was an increment in EPO concentration correlated to their severity of anemia in the most patients with hematological disorders, such as iron deficiency anemia (correlation coefficient r = -0.74), aplastic anemia (r = -0.89), leukemia (r = -0.81), and MDS (r = -0.65). On the other hand, EPO concentration in sera from all the untreated patients with polycythemia vera were significantly low level. But the concentrations of EPO from the patients successfully treated, with normal hematocrit were recovered to normal level. In the patients with secondary polycythemia, there were much varieties in EPO level. Assay of EPO in blood is important not only for diagnosis of polycythemia but also for the analysis of anemia and clinical use of EPO in vivo. The method described here is accurate and technically not complicated, and could be widely induced in most laboratories.
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PMID:[Assay of erythropoietin in serum with short term enzyme linked immunosorbent assay method--the clinical significance, Part 1: Relation to anemia in renal failure and hematological disorders]. 834 55

Philadelphia chromosome-positive essential thrombocythaemia (Ph(+)-ET) and chronic granulocytic leukaemia (Ph(+)-CGL) constitute a separate malignant disease entity, whereas essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic megakaryocytic granulocytic metaplasia (CMGM) belong to the Philadelphia chromosome-negative (Ph-) myeloproliferative disorders. The megakaryocytes in Ph(+)-ET and Ph(+)-CGL are abnormal and small with round nuclei, showing little lobulation. Both the number and size of megakaryocytes in Ph-ET, -PV and -CMGM are typically increased. Enlarged 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. In reactive thrombocytosis the size and morphology of increased megakaryocytes are normal. The characteristic increase and clustering of enlarged mature and pleomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses is the diagnostic hallmark of untreated PV. In secondary polycythaemia, in which increased cellularity of the erythroid cell line may be present, the number, size and morphology of megakaryocytes remain small and normal. CMGM, including early stages without myelofibrosis and advanced myelofibrotic stages of agnogenic myeloid metaplasia, appears to be a distinct neoplastic proliferation of neutrophilic granulopoiesis and megakaryopoiesis. The histopathology of the bone marrow in CMGM is dominated by atypical, enlarged and immature megakaryocytes with cloud-like nuclei which are not seen in ET and PV. Myelofibrosis in ET, PV and CMGM is graded in no reticulin fibrosis (MFO), early reticulin fibrosis (MF1), advanced reticulin sclerosis with minor collagen fibrosis (MF2) and advanced collagen fibrosis with or without osteosclerosis (MF3). Myelofibrosis is not a feature of ET, may occur in PV, and constitutes a prominent feature of CMGM during the natural history of the disease.
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PMID:Diagnostic criteria of the myeloproliferative disorders (MPD): essential thrombocythaemia, polycythaemia vera and chronic megakaryocytic granulocytic metaplasia. 928 42

Angiogenesis has been implicated in the growth, dissemination and metastasis of solid tumours. Several recent studies have shown increased bone marrow vasculature in acute and chronic leukaemia as well as in myelofibrosis and myelodysplastic syndromes. Increased serum and/or cellular levels of vascular endothelial growth factor (VEGF) as the most potent and specific angiogenic factor were reported in acute and chronic leukaemia and multiple myeloma and also predict poor prognosis in these haematological malignancies. Little is known about angiogenesis and VEGF levels in polycythemia. Thus, the serum levels of VEGF (pg/ml) and erythropoietin (U/l) were determined using ultra-sensitive ELISA assays in 16 polycythemia patients (10 with polycythemia vera (PV) and 6 with secondary polycythemia) and correlated with their clinical and laboratory features. The serum levels of VEGF were significantly higher in 90% of PV cases and 60% of secondary polycythemia compared to healthy controls. The median VEGF levels (pg/ml) were 622 (range, 272-4760), 306 (range, 111-408) and 143 (range, 91-282) in PV, secondary polycythemia and healthy controls, respectively. Since serum VEGF reflects both plasma VEGF and platelet released VEGF, the concentration of VEGF per platelet (VEGF/PLT) as pg per 10(6) platelet was used as a more standardised measure. Splenomegaly emerged as the main factor associated with a marked increase in serum VEGF/PLT levels. On the other hand, the serum erythropoietin levels (U/l) were significantly reduced in PV (range, 1.2-14.3) raised in secondary polycythemia (range, 26-104) compared with normal controls (range, 9.7-31.1), P<0.01. In conclusion, the present study shows increased VEGF levels in most polycythemia patients, and splenomegaly is associated with a profound increase in VEGF serum levels in these patients. Also, patients with PV have significantly reduced serum levels of erythropoietin compared with secondary polycythemia. Also, serum VEGF/PLT was higher in PV patients treated with phlebotomy alone rather than oral chemotherapy, suggesting a possible advantage for chemotherapy over phlebotomy alone in suppressing the disease progression. Further studies with large number of polycythemia cases are warranted to explore the role of these cytokines in the pathogenesis, diagnosis and/or therapy of polycythemia.
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PMID:Increased serum levels of vascular endothelial growth factor correlate with splenomegaly in polycythemia vera. 1236 69