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)

Using a short term liquid system we have shown that blood from some patients with primary myelofibrosis (PMF) and chronic granulocytic leukaemia (CGL) in megakaryoblastic transformation (CGL-Mk) gives rise to large numbers of progenitor cells committed to the megakaryocyte (Mk) lineage. As assessed by indirect immunofluorescence the number of cells reacting with three antiplatelet monoclonal antibodies, C17, J15 and AN51, increases during the culture period. There is no equivalent increase in cultures from the blood of normal individuals or patients with essential thrombocythaemia (ET). Furthermore plasma-free supernatants from cultures of the cells from patients with PMF and CGL-Mk stimulate the rate of proliferation of fibroblasts from normal bone marrow. These data provide further evidence for the involvement of the Mk lineage in PMF and CGL and suggest that the excess fibrosis seen in these conditions may be caused by a factor emanating from Mks.
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PMID:Proliferation in liquid culture of megakaryocytes from the blood of patients with primary myelofibrosis and other myeloproliferative disorders. 406 50

A murine monoclonal antibody (82H5, IgM class) has been developed that detects an antigenic determinant expressed by greater than 90% of normal granulocytes and 60-80% of light-density normal bone-marrow cells, including human pluripotential progenitors (colony-forming-unit-granulocyte, erythroid, macrophage, megakaryocyte; CFU-GEMM) and committed progenitors: granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and megakaryocytic (CFU-MK). This antibody did not react with erythrocytes, monocytes, platelets, lymphocytes from normal peripheral blood, lymphoblasts from patients with acute lymphoblastic leukaemia, or with lymphoid cells lines. The 82H5-defined antigenic determinant was expressed on greater than 90% of leukaemic cells of promyelocytic, myelomonocytic and monocytic morphology, and cell lines KG.1, ML.1, HL.60, K562 and U.937. Cortical thymocytes were unreactive with 82H5. Treatment of human bone-marrow cells with granulocytic-specific monoclonal antibody 82H5 plus complement significantly inhibited colony formation (48-74%; P less than 0.05) of CFU-GEMM, CFU-GM, BFU-E, CFU-MK, whereas treatment with control monoclonal anti-Ia antibody plus complement caused 79-89% inhibition. This antibody reacted strongly with 3-fuc-NAc lactosamine when tested with a panel of synthetic carbohydrate structures. We conclude that 82H5 may be a useful probe for phenotypic analysis of leukaemic cells and investigation of haematopoiesis.
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PMID:Monoclonal antibody specific for granulocytic-lineage cells and reactive with human pluripotent and committed haematopoietic progenitor cells. 620 78

The expression of glycoprotein I (GP I) on normal and pathological megakaryocyte (MK) precursors has been investigated in vivo and in a cell culture system with mouse monoclonal antibody (AN51) using immunofluorescence, immunogold and immunoferritin with electron microscopy. Our results confirmed the observation of Rabellino et al. (1979, 1981), using polyclonal antibodies, that GP I was expressed throughout normal MK maturation. The present result differs from our previous work which failed to detect binding of AN51 on promegakaryoblasts (PMKB). Improvement of immunofluorescent techniques has permitted detection of weak fluorescent labeling on normal PMKB by day 6-7 of in vitro culture from normal CFU-MK. An increased number of labeled PMKB was observed in bone marrow from patients with idiopathic thrombocytopenic purpura (ITP) as compared with normal bone marrow. In 20 selected cases of acute megakaryoblastic leukemia, AN51 labeled the PMKB but at a lower percentage than with J15 (monoclonal anti-glycoprotein IIb/IIIa complex). The MK nature of the blasts was confirmed by the ultrastructural detection of platelet peroxidase (PPO) and by the binding of AN51 demonstrated with immunoferritin-conjugated anti-mouse IgG. The immunogold technique revealed that the density of gold particles on the cell membrane of PMKB was variable, but generally weaker than in platelets or pathological micromegakaryocytes. The specificity of AN51 for MK lineage was shown by the absence of binding of AN51, by all blasts from 60 cases of acute leukemia involving other cell lines. Because of its weak labeling of PMKB due to the small number of antigenic sites, AN51 must be associated with another megakaryocytic marker in the diagnostic assessment of acute megakaryoblastic leukemia.
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PMID:Glycoprotein I identification during normal and pathological megakaryocytic maturation. 622 99

Sera from patients with aplastic anemia and amegakaryocytic thrombocytopenia contain an activity that stimulates megakaryocyte colony formation in vitro. We have assayed this megakaryocyte colony-stimulating activity (Meg-CSA) in sera of four patients receiving intensive antileukemic chemotherapy to determine whether the appearance of Meg-CSA is a physiologic response to the suppression of megakaryocytopoiesis. Three of the four patients were receiving consolidation or late intensification therapy for acute myoblastic leukemia (AML) in remission. The fourth was receiving induction therapy for de novo AML. During all or part of four chemotherapeutic cycles, serial Meg-CSA levels were assessed and correlated with the corresponding peripheral platelet counts. All courses of cytotoxic chemotherapy resulted in increases in serum Meg-CSA comparable to activity levels present in sera from patients with aplastic anemia. Two of the three patients studied during the early postchemotherapy interval manifested initial serum Meg-CSA elevations seven days before their thrombocytopenic nadirs when platelet counts were still between 100,000/mm3 and 140,000/mm3. Bone marrow recovery from chemotherapy was characterized by a decrease in serum Meg-CSA to pretherapy levels that occurred concurrently with the rise in platelet count to normal. These observations support the hypothesis that Meg-CSA is a physiologic humoral regulator of megakaryocytopoiesis elaborated in response to the depletion of either bone marrow megakaryocytes or megakaryocyte progenitor cells.
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PMID:Human serum megakaryocyte colony-stimulating activity increases in response to intensive cytotoxic chemotherapy. 633 51

Acute leukemia with megakaryocytic differentiation has been an uncommonly recognized disorder. We used specific monoclonal and polyclonal antibody reagents (HP1-1D antibody and anti-factor VIII antibody, respectively) and an immunocytochemical staining technique to identify the megakaryocytic nature of the leukemic cells of 12 patients who presented with acute leukemia. The leukemic cells of our patients demonstrated the presence of one or both of these platelet- and megakaryocyte-related antigens, but were negative for all of the commonly employed cytochemical and immunocytochemical staining reactions, except for diffuse acid phosphatase activity and granular PAS positivity. Morphologically, the leukemic cells varied in size from 10 to 40 microns in diameter, frequently had cytoplasmic budding, and contained occasional vacuoles and/or peroxidase-negative azurophilic granules. Five patients presented with syndromes of acute myelofibrosis, and seven patients had otherwise unclassifiable acute leukemias, including three patients who had secondary leukemias. Diffuse reticulin myelofibrosis was present in all cases in which it was sought. Chromosomal abnormalities of leukemic cells were found in five cases. Two patients had deficiencies of plasma coagulation factor V. Study of one patient revealed significant platelet dysfunction. When cytoreductive chemotherapy of leukemia was attempted, the observed response was generally poor, with the exceptions of one patient who has remained in complete remission following treatment with etoposide (VP-16) and a second patient who attained remission following bone marrow transplantation. These cases of acute megakaryoblastic leukemia represented from 3.6% to 9.3% of all acute leukemia cases diagnosed concomitantly in our institution. Acute leukemia with megakaryocytic differentiation may occur more frequently than previously recognized, may present with differing syndromic features, and can be identified by the use of specific antibody reagents and relatively simple immunocytochemical techniques.
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PMID:Acute leukemia with megakaryocytic differentiation: a study of 12 cases identified immunocytochemically. 637 77

The production of blood cells is a dynamic process that is noticeably aberrant during disease. The availability of colony assays in vitro that allow detection of hematopoietic stem and progenitor cells for the neutrophil, monocyte-macrophage, erythroid and/or megakaryocyte lineages has been of importance for the present understanding of the mechanisms controlling the proliferation, self-renewal capacity, and differentiation of morphologically nonrecognizable immature cells which give rise to the mature progeny circulating in the blood. It is through the use of these assays that the existence of potentially relevant stimulatory and inhibitory feedback interactions has been demonstrated. Abnormalities in these interactions, which may be of significance during leukemia and related disorders, have been uncovered. This communication will discuss regulatory interactions detected via the colony assays, their potential relevance physiologically and pathologically, and the use of these assays for diagnosis, prognosis, and for monitoring the clinical status of patients.
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PMID:Colony assays of hematopoietic progenitor cells and correlations to clinical situations. 639 66

Twenty cases of leukemia involving platelet precursors have been identified by a panel of monoclonal and polyclonal antiplatelet antibodies and by the ultrastructural demonstration of platelet peroxidase (PPO). The two techniques were in close agreement both for identification and for the quantitation of the blast cells except in three cases where PPO was present in the absence of the immunological markers. The immunological appearance of the leukemic megakaryocytic precursors was identical to that of their normal counterparts; the cells were positive with J 15 (anti GP IIb-IIIa complex), C 17 (anti GP IIIa), J 2 (anti GP 26,000) AN 51 (anti GP Ib). A diffuse cytoplasmic labelling was observed with anti factor VIII vwF and anti platelet factor 4 (PF 4). In addition, the leukemic maturation was quite similar to normal megakaryocyte differentiation since in micromegakaryocytes the expression of Gp Ib was strong and an intense granular pattern of labelling with anti factor VIII vwF and anti PF 4 was observed. In no case was the leukemic megakaryocytic series labelled by anti-erythroid antibodies, anti myeloid antibodies or J 5, B 1, OKT 11 antibodies. Using ultrastructural immunoferritin with J 15 it was possible to demonstrate that labelling with this antibody only occurred on PPO-positive cells. Immunogold or peroxidase labelling with AN 51 at the EM level in cases of mixed leukemia showed that Gp Ib was absent from proerythroblasts and myeloblasts. Therefore, in no case were specific platelet markers expressed in the leukemias of other cell lineages.
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PMID:Immunological characterization of the leukemic megakaryocytic line at light and electron microscopic levels. 649 54

To determine how alterations of megakaryocyte proliferation will affect platelet production, we measured mean platelet volume (MPV), platelet volume heterogeneity, platelet count, and mean megakaryocyte ploidy in 42 patients. In normal subjects, mean platelet volume and megakaryocyte ploidy were related inversely but nonlinearly to platelet count, whereas mean platelet volume and platelet volume heterogeneity were related directly. In patients with immune thrombocytopenic purpura (low platelet count, MPV above normal, and increased megakaryocyte ploidy), and in those with reactive thrombocytosis (high platelet count, low MPV and megakaryocyte ploidy), the relation of MPV to megakaryocyte ploidy, platelet volume heterogeneity, and platelet count resembled or extended the relations found in normal subjects. By contrast, in patients with aplastic anemia or megaloblastic anemia, or in patients who were undergoing chemotherapy for leukemia, heterogeneity was increased abnormally at any MPV, and both MPV and megakaryocyte ploidy were substantially lower, at any platelet volume, than in normals or the above other groups. The most common ploidy class was 8N in all patients, and the mean megakaryocyte ploidy correlated directly and linearly with mean platelet volume. The data show that bone marrow with megakaryocytes of higher ploidy produces platelets that are both larger and more heterogeneous.
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PMID:The relation of megakaryocyte ploidy to platelet volume. 653 64

The surface antigen phenotype of 30 patients with the blast phase of chronic myeloid leukemia (CML) was determined using a panel of monoclonal antibodies recognizing differentiation antigens of normal myeloid, erythroid, megakaryocyte, and lymphoid cells. Ten patients' cells expressed a phenotype corresponding to an immature myeloid cell and were felt to have "myeloid" blast crisis. None of these myeloid leukemias were TdT+ or responded to vincristine (V) and prednisone (P). Eleven patients expressed a phenotype similar to acute lymphoblastic leukemia cells and probably reflect maturation to an early B lymphocyte. All of these "lymphoid" leukemias were TdT+, and 67% of evaluable patients had a complete response to V and P. One leukemia had the phenotype of an erythroleukemia, one patient's cells expressed the phenotype of megakaryoblastic leukemia, and one leukemia had populations of both myeloid and lymphoid blasts. Six leukemias did not express surface markers characteristic of any lineage and were termed "undifferentiated." This group was heterogeneous with respect to TdT expression, but no patient had a complete response to V and P. Determination of surface antigen phenotype in CML blast crisis thus provides clinically useful information for the structuring of treatment protocols.
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PMID:Differentiation patterns in the blastic phase of chronic myeloid leukemia. 657 17

Factors that stimulate the proliferation and differentiation of murine bone marrow cells have been purified from a cloned T cell lymphoma, LBRM-33, and a cloned myelomonocytic leukemia cell line, WEHI-3. These colony-stimulating factors (CSF) have been purified by sequential fractionation by using salt precipitation, gel filtration, anion and cation exchange chromatography, and high pressure liquid chromatography. Both LBRM-33 and WEHI-3 cells secrete a CSF species with similar chemical and biologic properties. This CSF species appears to exist in two forms, termed CSF-2 alpha and CSF-2 beta, both of which stimulate the growth of bone marrow cells in the granulocyte, macrophage, megakaryocyte, mast cell, and erythrocyte lineages, as well as the growth of a CSF-dependent cell line, FDC-P2. These properties of CSF-2 alpha and -2 beta are similar to those reported for interleukin 3, hematopoietic cell growth factor, mast cell growth factor, and persisting cell growth factor. However, LBRM-33 cells secrete another CSF species, not produced by WEHI-3 cells. This CSF species, unique to LBRM cells, is termed here CSF-2 gamma and it stimulates the proliferation of granulocytes and macrophages from bone marrow but does not support the growth of FDC-P2 cells.
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PMID:Biochemical comparison of murine colony-stimulating factors secreted by a T cell lymphoma and a myelomonocytic leukemia. 660 83


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