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)

In this report we present the autopsy findings of acute megakaryoblastic leukemia with tumor formation in a 2-year-old female infant with Down's syndrome. Chromosomal analysis of blast cells revealed constitutional anomaly of trisomy 21 and two other related types of abnormal clones. Flow cytometric examination revealed blast cells expressing Ia-like or HLA-DR antigens. Postmortem examination showed extensive infiltration of leukemic cells in most of the examined organs, including the bone marrow with myelofibrosis. Tumor masses in the maxillary, frontal and femoral bones and the atria of the heart had undergone massive infiltration of atypical blast cells with an increase in the reticulin network. The final diagnosis was confirmed by ultrastructural cytochemistry of the platelet peroxidase reaction as well as by immunological staining utilizing anti-platelet glycoprotein IIb/IIIa, antiplatelet factor 4 and anti-beta-thromboglobulin antibodies for the blast cells. It seems likely that platelet-derived growth factor, secondary to an increase in the reticulin network, plays a major role in myelofibrosis of acute megakaryoblastic leukemia with tumor formation.
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PMID:Acute leukemia of megakaryocyte lineage with tumor formation. An autopsy case of patient with Down's syndrome. 296 53

Congenital absence of platelet glycoproteins IIb and IIIa (GPIIb and GPIIIa) results in a severe bleeding disorder characterized by defective platelet aggregation and failure of fibrinogen to bind to platelets. GPIIb is a two-chain protein containing disulfide-linked alpha and beta subunits. GPIIb and GPIIIa are present as a heterodimeric, noncovalent complex in the platelet plasma membrane and function as the fibrinogen receptor. To characterize synthesis of these two proteins, RNA isolated from a human leukemia cell line that contains GPIIb and GPIIIa was translated in a wheat germ cell-free system. Polyclonal antibodies specific for each protein immunoprecipitated distinct [35S]methionine-labeled precursors, indicating that GPIIb and GPIIIa are translated from separate mRNAs. Moreover, using specific antibodies against either intact unreduced GPIIb or the beta subunit, we obtained evidence for synthesis of a common polypeptide precursor for GPIIb alpha and GPIIb beta. Based on experiments using microsomal membranes, it appears that GPIIb is integrated into the platelet membrane with little or no cytoplasmic component. These results suggest that precursors of GPIIb and GPIIIa may be encoded by separate genes and that each precursor is processed before delivery to the plasma membrane.
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PMID:Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa. 300 53

Four case histories are reported: 1. A 37-year-old woman suffering from Glanzmann's thrombasthenia has been regularly seen since 1955. Characteristically (and in contrast to the first description by Glanzmann!) persistently prolonged bleeding times were noted. Clot retraction is severely diminished and the platelets fail to aggregate upon various stimuli. (Platelet agglutination upon addition of ristocetin to platelet rich plasma is normal.) The diagnosis of thrombasthenia was confirmed by demonstration of a deficiency of the membrane glycoprotein IIb/IIIa complex. In recent years the patient has become refractory to platelet transfusion therapy, a response shown to be due to antibodies against GPIIb/IIIa in the plasma. Spontaneous bleeding tendency has appeared to improve over the years. 2. Two patients with proliferation of B-lymphocytes are presented. a) Splenomegaly and an increase of B-lymphocytes in the peripheral blood were detected in a 45-year-old asymptomatic man. DNA analysis suggested that polyclonal proliferation of B-lymphocytes was present. Diagnostic considerations are discussed. b) In a 46-year-old male patient with subacute aleukemic leukemia of a pre-B-cell type diagnosed in 1981, the disease showed an unexpectedly benign course: after initial mild chemotherapy the patient has remained in a stable condition while off cytotoxic treatment for the last two years. Nevertheless, besides anemia necessitating regular transfusions, persistent agranulocytosis is present which is not explained by bone marrow infiltration. In vitro experiments suggest suppression of myelopoiesis by cellular interaction with leukemic cells or a deficiency of growth factors causing agranulocytosis. 3. An 81-year-old man showed signs and symptoms of lead intoxication which proved to be due to oral ingestion of a lead-containing ointment.
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PMID:[Unusual features in Glanzmann thrombasthenia; proliferation of B-lymphocytes, lead poisoning]. 305 86

The clinical, hematologic, and phenotypic features of 28 patients with acute leukemia with megakaryocytic involvement (AMKL) were analyzed. The prevalence of this type of leukemia in the entire series was 11.6%, with a higher incidence among patients with acute transformation of a previous myeloproliferative disorder (MPD) (24%) than among the transformed myelodysplastic syndrome (13%) patients. The incidence in the "de novo" ANLL was 8% and 16% among secondary leukemias. The presence of bone marrow fibrosis together with low WBC and normal or increased platelet counts despite a severe anemia are the most relevant features in these patients who otherwise displayed an apparently poor prognosis. Megakaryoblasts were morphologically recognized more frequently in the acute transformations of MPD than in de novo ANLL. Only two cases were considered pure AMKL, and in the remaining 26 patients, megakaryoblasts coexisted with other granulomonocytic and/or erythroid populations. Antiglycoprotein IIIa (anti-GPIIIa) (C17) and anti-GPIIb/IIIa (CDw41-, J15-) antibodies are probably the best markers for AMKL, although the monoclonal antibody against GPIX (FMC25) was also positive in a majority of cases but in a lower percentage of cells. On the other hand, megakaryoblasts were generally negative for granulocytic or monocytic markers (CD13, CD14, CD15); the expression of HLA-DR antigens in these cells was variable. Our present results indicate that megakaryoblastic involvement is more common than previously recognized. This is true not only in acute transformed leukemias but also in de novo ANLL. Although the diagnosis of these cases should be based on megakaryocytic markers, it is often possible to suspect a diagnosis according to certain clinical and hematologic features.
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PMID:Leukemias with megakaryoblastic involvement: clinical, hematologic, and immunologic characteristics. 316 92

A new human megakaryocytic cell line (Dami) has been established from the blood of a patient with megakaryoblastic leukemia. The Dami cells grow primarily in suspension with a doubling time of 24 to 30 hours. By light and electron microscopy, the Dami cells range in size from 12 to 120 micron in diameter and have lobulated nuclei characteristic of megakaryocytes. At least 89% of the cells react with monoclonal antibodies against platelet glycoproteins (GP) Ib and IIB/IIIa, and glycophorin. The cells do not react with antibodies against lymphoid, monocyte, granulocyte, or macrophage antigens. Thirteen percent of the cells become polyploid, spontaneously achieving greater than 4N DNA ploidy levels. In response to phorbol myristate acetate (PMA), the proportion of cells with ploidy levels greater than 4N increased threefold and could be separated into discrete ploidy groups. PMA also increased the expression of GPIb, the GPIIb/GPIIIa complex,l and von Willebrand factor. Cytogenetic analysis revealed a human male hyperdiploid karyotype with a modal chromosome number of 54 to 64 and several consistent clonal chromosomal abnormalities. These included a partial deletion of chromosome 5 and a translocation involving chromosome 3. In contrast to other megakaryocytic cell lines in which only a small portion of the cells express the megakaryocytic phenotype, nearly all of the Dami cells express platelet glycoproteins. Thus, the Dami cells provide a superior model in which to study human megakaryocyte biochemistry and differentiation.
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PMID:Characterization of a new megakaryocytic cell line: the Dami cell. 319 74

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

A panel of 19 monoclonal antibodies (McAb) and the enzyme terminal transferase (TdT) have been applied to the characterization of poorly differentiated blasts from 50 patients with chronic granulocytic leukaemia (CGL) and myelofibrosis in blast crisis (BC), acute myelofibrosis and undifferentiated leukaemia. These cells were also extensively studied by transmission electron microscopy (TEM) (see Polli et al, 1985a). McAb against platelet glycoproteins (GP) showed a high specificity for megakaryoblasts, in particular those reactive with the GPIIb/IIIa complex (J15) and GPIIIa (C15 and C17), which were positive in a higher proportion of blasts than the McAb to GPIb (AN51 and FMC25). Findings with these anti-platelet McAb paralleled those of the platelet-peroxidase (PPO) reaction in 76% of cases studied simultaneously. The PPO reaction was always positive in cases in which two or more of the McAb were reactive with the blast cells. The differences observed suggest, nevertheless, that PPO is more sensitive for megakaryoblasts than the McAb and that this TEM technique should be reserved for cases which are negative with the platelet specific McAb. Of the McAb against myeloid antigens used in this series OKM1 was positive in 50% of cases but the others failed to demonstrate early features of differentiation in myeloblasts and monoblasts. In only three cases were erythroid precursors demonstrated by TEM and these were the only ones reactive with a McAb to glycophorin-A (LICR LON/R10). TdT and the McAb J5 helped in the identification of lymphoblasts which were seen as a 'pure' proliferation in 23% of CGL-BC and as part of blast cell mixtures in another 17% of cases. The McAb reactive to haemopoietic precursor cells (RFB1, FMC8 and OKIa), on the other hand, were of no practical value for the classification of blast cell types. The lineage specificity of several of the McAb used in this study, confirmed by TEM, suggest that these reagents are valuable tools for the characterization of immature blast cells.
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PMID:Characterization of blast cells in chronic granulocytic leukaemia in transformation, acute myelofibrosis and undifferentiated leukaemia. II. Studies with monoclonal antibodies and terminal transferase. 388 37

Ultramicroscopic membrane vesicles were found in the plasma of 17 patients with certain types of leukemia (acute promyelocytic leukemia, acute monocytic leukemia, acute myelomonocytic leukemia, and chronic myelogenous leukemia) and in guinea pigs with the L2C leukemia. Labeled vesicles were cleared from normal guinea pig plasma according to a two exponential function with a half-life for the second exponent of greater than 11 h. By immunofluorescence, vesicles shared antigens with the L2C leukemic cells. Attempts to elucidate the cellular origin of the circulating vesicles in human leukemias were less definitive. However, vesicles did not react with the platelet membrane antigen GP IIb/IIIa nor did the presence of circulating vesicles or vesicle-associated procoagulant activity correlate with the platelet count. In three patients studied serially, circulating vesicles paralleled disease activity. Vesicles were not detected in 16 other patients with leukemias including acute myelogenous leukemia and most lymphoid leukemias. Similarly, vesicles were not present in 29 normal plasmas or in 10 plasmas from patients with solid tumors or nonmalignant hematological disorders. In contrast to vesicles of similar appearance shed by a variety of solid and ascites tumor cells in vitro and in vivo, the vesicles circulating in leukemia patients and guinea pigs expressed variable and generally weak procoagulant activity and no tissue factor activity. Thus, although many of the patients with circulating vesicles expressed abnormal coagulation, we were not able to establish a close pathogenetic relationship between the procoagulant activity of circulating vesicles and clinical coagulopathies.
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PMID:Circulating membrane vesicles in leukemic blood. 405 66

The human proerythroblastic leukemia cell-line K562 was induced to differentiate into megakaryocytic cells by 12-O-tetradecanoylphorbol-13-acetate (TPA). Megakaryocytic differentiation was detected when lineage-specific monoclonal antibodies were used to monitor the effect of TPA on K562 cells. A monoclonal anti-platelet antibody (C17) directed against an epitope present on GP IIIa appeared to react with K562 cells after induction. This was observed together with the disappearance of glycophorin A, the erythrocyte-specific lineage antigen. The induced megakaryocytic cells were also detected by ultrastructural platelet peroxidase (PPO). Immunoprecipitation, after ectolabeling of the cells with the C17 antibody and SDS-polyacrylamide gel electrophoresis, proved that TPA-induced K562 expressed both GP IIIa and GP IIb. However, the monoclonal antibody C15 directed against another epitope of platelet GP IIIa reacted only partially, or not at all, indicating that GP IIIa expressed on TPA-induced K562 differs structurally from that on normal platelets. K562 clones, expressing glycophorin A in all cells, were obtained by limiting dilution and culture. When these clones were treated with TPA, again megakaryocytic cells were obtained. These findings are discussed in relation to normal megakaryocytopoiesis.
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PMID:Megakaryoblastic differentiation of proerythroblastic K562 cell-line cells. 623 32

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


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