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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association between leukemic transformation and various features recorded at presentation in patients with refractory anemia with excess of blasts and with or without ringed sideroblasts was analyzed in 255 patients using the proportional hazard model. Features associated with higher transformation rates were: higher values of blasts in peripheral blood or bone marrow; serum haptoglobin; vitamin B12; megakaryocytes in bone marrow; morphological abnormalities in granulo- or megakaryocyte series; male sex; circulating megakaryocytes in peripheral blood; older age; and lower ringed sideroblast proportion. Multivariate analysis was also performed using the following predictor variables: presence or absence of refractory anemia with excess of blasts; sex; abnormal granules in granulocytes; age; and mononuclear large megakaryocytes. Patients were divided arbitrarily into low (hazard ratio, less than 0.45), intermediate (hazard ratio, 0.45-1.85) and high (hazard ratio, greater than 1.85) risk groups. The cumulative leukemia-free rates in the low and intermediate risk groups showed long plateau phases at 95 and 71%, respectively, while in the high risk group, the rate was 10% at 5 years. For clinical purposes, the low risk group should be considered to have nonpreleukemia and the high risk group to have preleukemia.
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PMID:Factors influencing leukemic transformation in refractory anemias with excess of blasts, with ringed sideroblasts, and without ringed sideroblasts. 345 28

The level of urinary Meg-CSF activity in patients with various thrombopoietic disorders was studied. Five out of eight patients with idiopathic thrombocytopenic purpura had megakaryocytic hyperplasia in the marrow and increased Meg-CSF activity in the urine. Urinary Meg-CSF activity in patients with polycythaemia vera and essential thrombocythaemia was normal. There was a significant inverse correlation between urinary Meg-CSF activity and peripheral blood platelet count but not bone marrow megakaryocyte mass. There was a significant increase of urinary Meg-CSF activity during the period of thrombocytopenia after chemotherapy in patients with acute leukaemia who were in complete remission. The timing of maximal Meg-CSF levels corresponded to the nadirs of platelet counts. These results support the concept that Meg-CSF may play a significant role in the regulation of megakaryopoiesis and/or thrombopoiesis in vivo.
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PMID:Human urinary megakaryocyte colony-stimulating factor in thrombopoietic disorders. 348 93

A case of blast crisis in chronic myelogeneous leukaemia (CML) in which two distinct cell lineages were involved is presented. The phenotype of blasts in lymph nodes was T11 (CD2)+, Ia+, TdT+, suggesting T cell lineage. On the other hand, blasts in bone marrow and peripheral blood expressed platelet glycoprotein IIb/IIIa complex on their surface, suggesting megakaryocyte lineage. Cytogenetic analysis of lymph node and bone marrow cells revealed the abnormalities, inv(7) (p15q34) and t(1;3) (q23;q21), respectively, as well as the presence of the Ph1 chromosome in both cell types. Rearrangement of the T cell receptor beta-chain gene was detected in lymph node blasts, although blast cells in peripheral blood showed a germ line configuration. The involvement of T cell and megakaryocyte lineages in the blast crisis phase of CML was confirmed in our phenotypic and genotypic analysis, and the pathogenic association between blast crisis lineages and the additional chromosome abnormalities present is discussed.
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PMID:Phenotypic and genotypic analysis of chronic myelogenous leukaemia with T lymphoblastic and megakaryoblastic mixed crisis. 349 65

The authors present a patient with the typical clinical picture of an acquired amegakaryocytic thrombocytopenic purpura. After 16 months of observation, the patient developed acute myelomonocytic leukemia. During the preleukemic phase and after progression to overt leukemia, serial in-vitro analyses of megakaryocytic, granulocytic, erythrocytic and T-lymphocytic colony growth were carried out in a microagar culture system. At presentation, a marked diminution of CFU-M was observed, whereas CFU-E, BFU-E, CFU-C and CFU-TL were in the normal range. The CFU-M number remained at its low level during the whole observation period. The CFU-C number declined steadily during the preleukemic period, while BFU-E, CFU-E and CFU-TL remained constant until January 1985 when the patient developed AML. After progression to overt leukemia, a distinct reduction became evident in all colony-forming cells. Cytogenetic studies performed during the preleukemic phase indicated the presence of a 5q- chromosome. The authors submit evidence here that the patient was not only characterized by defective megakaryocytic colony formation but also by a deficiency of functional megakaryocyte colony-stimulating activity. No humoral or cellular inhibitors of CFU-M colony formation were found. It is concluded that in preleukemia with a 5q- chromosome the megakaryocytic cell lineage may be involved in the process that precedes overt leukemia at an earlier time than cells of granulocytic and erythrocytic lineages. In addition, it is shown here that megakaryocytopoiesis during the preleukemic period can be characterized by two different defects: first, an intrinsic megakaryocytic stem cell defect and, second, a deficiency of functional megakaryocytic colony-stimulating activity.
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PMID:Progressive preleukemia presenting amegakaryocytic thrombocytopenic purpura: association of the 5q- syndrome with a decreased megakaryocytic colony formation and a defective production of Meg-CSF. 349 97

It is apparent that multiple cellular stages and biologic processes can be identified during megakaryocytopoiesis that are potentially subject to control by hematopoietic growth factors and marrow accessory cell populations. Two classes of megakaryocyte progenitor cells, the colony forming unit-megakaryocyte (CFU-MK) and the burst forming unit-megakaryocyte (BFU-MK), have now been detected in normal human bone marrow cells. The BFU-MK by virtue of the greater cellular content of its resultant colonies and the delayed time of appearance of these colonies appears to be a more primitive progenitor cell with a greater proliferative potential than the CFU-MK. A number of hematopoietic growth factors including megakaryocyte colony stimulating factor, (MK-CSF), recombinant erythropoietin (EPO) and granulocyte macrophage colony stimulating factor (GM-CSF) are each capable of increasing cloning efficiency of human megakaryocyte progenitor cells. It is presently unknown whether these factors act directly on the CFU-MK or whether they stimulate marrow accessory cells to elaborate growth factors that influence CFU-MK proliferation. In order to answer this question, the effect of these growth factors on the cloning efficiency of a human megakaryocytic cell line, EST-IU, was examined. Each of these factors was capable of increasing leukemia cell colony formation. One can conclude from these studies that MK-CSF, EPO, and GM-CSF act directly on cells of the megakaryocytic lineage. The physiologic significance of the lineage nonspecific effects of EPO and GM-CSF on megakaryocytopoiesis is yet to be determined. On the basis of these observations, a model of human megakaryocytopoiesis was suggested. Several factors appear able to influence multiple steps in megakaryocytic development, whereas others influence only specific stages or cellular events occurring during megakaryocytopoiesis.
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PMID:New insights into the regulation of human megakaryocytopoiesis. 349 96

The in vitro biological activities of thrombopoietic stimulating factor, recombinant interleukin 3, and megakaryocyte potentiator from various sources were studied. Growth activities were assessed by the responsiveness of enriched populations of small, immature megakaryocytes to factor preparations by measuring increased numbers of acetylcholinesterase-positive cells and increased cell size as indices of megakaryocyte development. All factors stimulated optimum megakaryocyte growth at high concentrations. Immature megakaryocytes revealed the same responsiveness to titrated amounts of the various factors tested, with similar slopes to the dose-response curves. The activities of both thrombopoietic stimulating factor and megakaryocyte potentiator were additive when suboptimal doses were used. In contrast, low concentrations of recombinant interleukin 3 and thrombopoietic stimulating factor acted synergistically to stimulate an optimal response. The data indicate that at low and perhaps physiologically relevant concentrations, two classes of factors influence murine megakaryocyte development by different but related mechanisms.
Leukemia 1987 Nov
PMID:Immature megakaryocytes in the mouse: synergistic response to megakaryocyte potentiator, thrombopoietic stimulatory factor with interleukin 3. 350 Mar 75

Several platelet function abnormalities have been described in the myeloproliferative syndromes. We have measured the intraplatelet vWF:Ag and fibrinogen (FI) in the platelet lysates by Laurell technique in 11 patients with polycythemia vera (PV), 10 with essential thrombocythemia (ET), 14 with chronic myelocytic leukaemia (CML) and 3 with myelofibrosis (MF) and these results were correlated with platelet function abnormalities. Decreased intraplatelet levels of vWF:Ag and FI were found in all the patients with ET and MF, in 8 out of 11 PV and 3 out of 14 CML. A statistical significant correlation was observed between the intraplatelet levels of vWF:Ag and FI in the control group and in CML and PV, but no correlation was found in ET and MF. No correlation was observed between the plasmatic and the intraplatelet levels of vWF:Ag and FI in any group. Evidences of platelet activation (spontaneous platelet aggregation or circulating platelet aggregates) were observed in 40% of the cases with ET and PV, and all these cases had low intraplatelet levels of both antigens. None of the cases with MF had evidences of platelet activation and 2 out of 14 patients with CML had platelet activation. The deficiency of the dense bodies was less frequent than the depletion of the alpha granules (5 out of 11 PV, 4 out of 10 ET, 6 out of 14 CML and 2 out of 3 MF). The low intraplatelet contents of vWF: Ag and FI, more frequently observed in ET and PV, may be the result of platelet activation and in vivo release, but megakaryocyte dysfunction is more likely in myelofibrosis.
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PMID:Intraplatelet levels of vWF:Ag and fibrinogen in myeloproliferative disorders. 350 18

The leukemic cells from 15 cases of Philadelphia chromosome-positive blastic leukemia were immunophenotyped by the alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemical technic using nine monoclonal antibodies (MoAb) reactive with various myeloid or lymphoid antigens. On the basis of morphology, cytochemistry, terminal deoxynucleotidyl transferase (TdT) reactivity, and electron microscopy, five of the cases had been classified as lymphoid; eight, myeloid; one, mixed myeloid-lymphoid; and one, undifferentiated. The blasts from all five lymphoid cases were reactive with lymphocyte differentiation antigen MoAb, and four of five reacted with MoAb to anti-common acute lymphoblastic leukemia-associated antigen (CALLA) (BA3). The blasts from all eight myeloid cases were reactive with MY7, a marker of myelomonocytic differentiation. Some of the blasts from three of the eight myeloid cases reacted with HP1-1D and AP3, markers of megakaryocytic differentiation; megakaryocyte differentiation was confirmed by electron microscopy. In the case classified as mixed myeloid-lymphoid, the blasts showed morphologic and immunophenotypic heterogeneity; ultrastructural studies demonstrated lymphoid, basophil, and erythroid differentiation. The blasts from the case classified as undifferentiated were immunophenotypically heterogeneous. In all cases in which the leukemic cells were also immunophenotyped by flow cytometry, the results correlated well with those obtained by the APAAP technic. The APAAP technic is a reliable method for immunophenotyping leukemias. Advantages of this method include its applicability to routinely prepared blood and bone marrow smears and cytocentrifuge preparations, lack of endogenous peroxidase background staining, and a permanent record.
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PMID:Monoclonal antibody study of Philadelphia chromosome-positive blastic leukemias using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technic. 351 97

In conclusion, a culture system is now available that reproducibly facilitates the development of megakaryocyte colonies and the emergence of megakaryocytes within multilineage colonies. The assay is dependent upon the use of human plasma and a source of exogeneous MEG-CSA. Patients with perturbed hemopoiesis plasma may contain activities able to replace exogeneous MEG-CSA. This system can therefore be used to evaluate MEG-CSA activities. In addition it is now feasible to study blast populations of patients with leukemia characterized by a megakaryocyte phenotype.
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PMID:Human megakaryocytopoiesis in cell culture. 390 Oct 29

Megakaryocytopoiesis was investigated with a polyclonal (26 cases) and a monoclonal (20 cases) antibody to factor-VIII-related antigen (factor VIII RAg) with the indirect peroxidase-antiperoxidase (PAP) method on air-dried bone marrow aspirates (BM). Numerous megakaryocyte precursors were identified in 5 patients with essential thrombocythemia (ET) and the 2 patients with acute myelogeneous leukaemia (AML) after recovery from therapeutic aplasia. Small megakaryocyte precursors were rare in controls (C), patients with reactive thrombocytosis (RT) and immune thrombocytopenia (IT). In 2 patients with severe alcoholism the number of mature megakaryocytes increased after 5 and 7 days of abstinence, respectively.
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PMID:Megakaryocytopoiesis in different forms of thrombocytosis and thrombocytopenia: identification of megakaryocyte precursors by immunostaining of intracytoplasmic factor-VIII-related antigen. 393 62


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