Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 22 patients with acute myeloid leukaemia (17 cases of myeloblastic leukaemia, 4 cases of myelomonocytic leukaemia and 1 case of undifferentiated-cell leukaemia) platelets were isolated from the plasma by the method of Nicholls and Hampton as modified by Levy-Toledano by centrifugation in albumin gradient. The aim of platelet isolation was their "concentration" in cases of thrombocytopenia to values making possible aggregation tests, and platelet separation from the influence of plasma factors. Then aggregation of isolated platelets caused by ADP was studied. In 16 out of 22 patients a fall of aggregation was observed, with the mean values of aggregation rate and intensity were significantly lower. Parallelly done determinations of aggregating activity released from the platelets by thrombin showed lower values as compared with platelets from healthy subjects. In might be thought, in this connection, that the demonstrated reduction of isolated platelets is associated with a diminution of the nucleotide pool or disturbances of the platelet release reaction. The disturbances of the platelet release reaction. The disturbances of aggregation of isolated platelets and reduction of the aggregating activity were most pronounced in acute myelomonocytic leukaemia.
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PMID:[Platelet function in acute myeloid leukemia. II. Aggregation of isolated platelets]. 28 Oct 86

Abnormalities in platelet dense granules, small intracellular organelles containing ATP, ADP, calcium, serotonin, and pyrophosphate, have frequently been reported in patients with leukemia and myeloproliferative disorders, particularly acute and chronic myelogenous leukemia. Recent studies of a family which includes several members with an autosomal dominant dense granule deficiency condition show an association between the presence of this form of dense granule deficiency and the development of acute myelogenous leukemia. Studies in two additional patients, one with the Monosomy 7 syndrome and the second with a myelodysplastic syndrome, revealed a defect in platelet dense granules. This defect appears to be due to an abnormality in the formation of these granules rather than the presence of empty vesicular structures or decreased contents due to activation associated secretion. The results suggest that the defect in platelet dense granules associated with leukemia or myelodysplastic syndromes may result from a chromosome alteration in the megakaryocyte cell line leading to decreased formation of dense granules. Studies in the family with an inherited bleeding disorder suggest that a gene coding for a protein important for the formation of dense granules is located adjacent to a gene which, when abnormal, may predispose to the development of leukemia.
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PMID:Platelet storage pool deficiency, leukemia, and myelodysplastic syndromes. 129 Sep 57

We investigated functional interactions between granulocyte-monocyte-colony-stimulating factor (GM-CSF) and the insulin family hormones using the GM-CSF- and insulin-dependent human acute myeloid leukemia cell line AML-193. Recombinant human GM-CSF and insulin enhanced AML-193 cell proliferation 3- and 5-fold, respectively, and showed a synergistic 10-fold increase when added in combination. Insulin-like growth factors I and II (IGFI and IGFII) increased AML-193 cell proliferation 4-fold and 2-fold, respectively, and also demonstrated synergy when combined with GM-CSF. Blocking experiments with monoclonal antibodies against the insulin and IGFI receptors indicated that the proliferative effects of insulin and IGFI were mediated through both their homologous and heterologous receptors. Pertussis toxin and cholera toxin, which ADP ribosylate GTP-binding proteins (G proteins), and the cyclic AMP analogue, dibutyryl cyclic AMP, decreased the proliferation induced by GM-CSF or insulin. Specific receptor binding of 125I-insulin, -IGFI, and -GM-CSF to AML-193 cells was demonstrated and not affected by preincubation with pertussis toxin or cholera toxin. Radiolabeled GM-CSF, insulin, and IGFI did not cross-compete with the heterologous ligands for receptor binding. These studies demonstrate (a) association between receptor binding and proliferative effects of GM-CSF and the insulin family hormones, (b) involvement of the G proteins in signal transduction provoked by these hormones which occurs at a postreceptor-binding level, and (c) synergistic mitogenic interactions between GM-CSF and the insulin family hormones, suggesting that their receptors are linked to divergent signaling mechanisms in addition to sharing G protein-coupled pathways.
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PMID:Functional interactions between colony-stimulating factors and the insulin family hormones for human myeloid leukemic cells. 169 37

Freshly isolated human peripheral blood lymphocytes from leukemia (AML, ALL, CML) subjects, showed a 2.5-3.5-fold increase in the poly ADPR transferase (poly ADPRT) activity whereas ovarian cancers showed a 2-fold increase. This was accompanied by a drop in NAD levels of 45%-63% in leukemia cells and 40% in ovarian cancers. Tumour promoters phorbol-12-myristate-13-acetate (PMA) and mezerein produced an increase in poly ADPRT activity in both normal and CML lymphocytes, but the increase was more marked in the case of normals. This was accompanied by a drop in NAD levels. The results presented show a marked increase in poly ADP-ribosylation in malignant cells but normal lymphocytes showed a greater response to tumour promoters as compared to CML lymphocytes.
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PMID:Enhanced poly ADP-ribosylation in human leukemia lymphocytes and ovarian cancers. 190 97

A family with an inherited bleeding disorder extending over four generations, and multiple cases of myeloblastic and myelomonoblastic leukaemia was studied. Ten members of the family had, by history, a haemorrhagic diathesis. There were three documented cases of myeloblastic leukaemia, two documented cases of myelomonoblastic leukaemia and two more cases of leukaemia by history. In four of the cases the bleeding diathesis clearly antedated the leukaemia, in two by many years. The bleeding disorder is characterized by a long bleeding time, abnormal platelet aggregation, low platelet ADP and decreased numbers of platelet dense bodies consistent with a dense granule storage pool deficiency. The number of dense granules was decreased by immunofluorescence employing quinacrine or using an antibody to the dense granule membrane protein, granulophysin, confirming an absolute decrease in dense granule numbers rather than the presence of empty granule sacs. This congenital storage pool deficiency is associated with a high incidence of acute myeloid leukaemia in this family.
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PMID:Inherited platelet-storage pool deficiency associated with a high incidence of acute myeloid leukaemia. 195 83

The levels of adenosine diphosphate ribosyl transferase (ADPRT) have been quantified in Ficoll-Isopaque isolated marrow cells from 36 patients with acute myeloid leukemia (AML). The in vitro growth pattern in agar at diagnosis was also determined, and in 16 patients the in vitro drug sensitivity of the clonogenic cells (CFU-GM) to cytosine arabinoside and daunorubicin was measured. The ADPRT activities of the various marrow cell preparations correlated to the morphological diagnoses, in vitro growth patterns, in vitro drug sensitivities to cytosine arabinoside, and to the prognoses of the AML patients. Hence, ADPRT may be a useful marker for the pathophysiology associated to AML.
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PMID:Adenosine diphosphate ribosyl transferase in marrow cells of patients with acute myeloid leukemia is related to differentiation and drug sensitivity. 299 Jul 54

Platelets frozen in glycerol-glucose frequently aggregated on thawing or reconstitution. This has been eliminated by using a nonplasma diluent (pH 6.5) and a new freezing bag. The results were improved platelet 14C-serotonin uptake and readily demonstrable aggregation to ADP, epinephrine, collagen and thrombin. 14C-serotonin uptake was at maximum when platelets were frozen at thrombocrits of up to 15%. Hemostatic effectiveness was demonstrated in a severely thrombocytopenic patient with acute myelogenous leukemia in relapse, who was supported entirely with two autologous frozen platelet transfusions for the 13 days before bone marrow activity resumed.
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PMID:Improved procedure for platelet freezing. 346 16

The red cell pyruvate kinase (PK) activity, KM for phosphoenolpyruvate (PEP) and adenosine diphosphate (ADP), and thermostability properties were studied in patients with acute leukemias. The acquired PK defect was found in patients with acute myeloid leukemia, while it was normal in acute non-myeloid leukemia enzyme kinetic tests. PK abnormality was expressed in 17 patients as deficient PK activity, in 15 patients as decreased enzyme thermostability, and in 11 patients as altered PK affinity for ADP.
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PMID:Red cell pyruvate kinase in acute leukemia. 651 Apr 4

Bleeding time, clot retraction, platelet factor 3 availability and platelet aggregation in response to ADP, epinephrine, collagen and ristocetin were studied in 13 cases of acute leukemia which included 5 cases of acute myeloid leukemia, 2 of chronic myeloid leukemia in blast crisis and 6 of acute lymphoblastic leukemia. More than one abnormality was seen in all the patients. Defects in bleeding time, clot retraction and platelet factor 3 availability were encountered in 43% of cases. Platelet aggregation responses to all the reagents were significantly impaired. There was, however, no consistency in the pattern of the defects.
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PMID:Platelet function in acute leukemias. 800 78

Human granulocyte-macrophage colony stimulating factor (GMCSF) and its high affinity receptor function to regulate the proliferation and differentiation of myeloid lineage hematopoietic cells, and may participate in the pathogenesis of many malignant myeloid diseases. We have used genetic engineering based on the elucidated molecular structures of human granulocyte-macrophage colony-stimulating factor and diphtheria toxin (DT) to produce a recombinant fusion toxin, DTctGMCSF, that targets diphtheria toxin to high affinity GMCSF receptors expressed on the surface of blast cells from a large fraction of patients with acute myeloid leukemia (AML). DTctGMCSF was specifically immunoreactive with antidiphtheria toxin and anti-GMCSF antiseras, and exhibited the characteristic catalytic activity of diphtheria toxin, catalyzing the in vitro ADP-ribosylation of purified elongation factor 2. The cytotoxic effects of DTctGMCSF were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium (MTT) bromide assay of cell viability and in vivo assays of protein synthesis inhibition. DTctGMCSF were specifically cytotoxic to human leukemia cell lines bearing high affinity receptors for human GMCSF with IC50 of 10(-9) to 10(-11) M. It was not toxic to mammalian hematopoietic cell lines lacking human GMCSF (hGMCSF) receptors. In receptor positive cells, cytotoxicity can be specifically blocked by a large excess of hGMCSF, confirming that its cytotoxicity is mediated through the hGMCSF receptor. THough DTctGMCSF inhibited granulocyte-macrophage colony formation by committed myeloid progenitor cells (CFU-GM), it did not significantly affect erythroid burst formation by committed erythroid progenitor cells (BFU-E), or mixed granulocyte-erythroid-macrophage-megakaryocyte colony formation by pluripotent multilineage progenitor cells (CFU-GEMM). DTctGMCSF holds promise for the treatment of myeloid lineage malignancies, and is a useful reagent to study hematopoiesis.
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PMID:A recombinant fusion toxin targeted to the granulocyte-macrophage colony-stimulating factor receptor. 916 36


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